Understanding Neuron Function and Signaling

Okay, neurons are similar to muscle cells in the sense that they're going to be able to send an impulse. They're able to communicate. They are excitable tissues. So we're going to see the cell membrane again. So to review, remember the inside of a normal cell is negative. reasons why. The sodium potassium pump. For every two positive that you bring in, you have to give up three positive. So that's like getting two dollars, but you have to give up three. Puts you at a negative. Cell membranes always have a small potassium leak, so there's a lot of potential for a small potassium leak. there are doors that are always open from the inside out to lose potassium. Just like I said, you may have a crack under your door where you lose a lot of air conditioning or lights able to get through. So we always lose positive K, therefore that's at a negative. And all the junk inside the cells, all the organelles, the DNA and RNA, the proteins, everything else, negative. So this results in a negative normal inside. But this is good because we want to create a reason, remember, for sodium to want to come in. Yeah. As soon as those doors open, because of acetylcholine opening the door, the neurotransmitter being the key, sodium wants in because there's lots of sodium outside the cell, and diffusion always tells us we want to go from where we're crowded to where we're not, and opposites attract. All that sodium wants to be with all that negativity. So we call this the electrochemical gradient. So this is a review for muscles. Chemical and electrical factors determine where ions want to go. So diffusion being chemical, the electrical being opposite. it's a tract. So remember, negative 70 is the number that I want you to know. So neurons are negative 70 at rest. Millivolts, one one-thousandth of a volt. So anytime you see that little negative sign, that's referring to the inside of the cell. So we saw this with muscles. Okay, so where things get kind of new. This little drawing here is on a body, the cell body, or on the dendrites. So on the cell body and dendrites, we have what are called chemically gated channels. And that's what we're going to call them. Technically they also call them ligand gated channels, but ligand just means chemical. So chemically gated channels. So we're going to see two different kinds of doors, chemically gated and voltage gated. So on the cell body and dendrite are chemically gated channels. The right chemical opens the door. So we've already seen these with acetylcholine. So these are acetylcholine sits there like a key and opens the door so a chemically gated channel So this happens on the cell body and on the dendrites on the axon though Which again is what I was just trying to draw there on the axon on are voltage-gated channels. And these are like those little key fobs that a lot of people have on their cars where they click that and it goes beep, beep, and it opens the door. You didn't have a physical key opening the door, the right voltage opened the door. So, On the dendrites and cell bodies, you have chemically gated channels, where a neurotransmitter has to physically open the door. On the axon, voltage gated. Now, we're going to see they open at negative 60. So that's another number we need to know. So a cell is negative 70 at rest, and these axon gates open at negative 60. So if I am negative 70 in my checking account, and I need to get to negative 60, I need 10 bucks. So we need enough sodium. sodium is positive. We need enough sodium to rush in to get us a 10 change to get these gates to open. So chemically gated versus voltage gated. So on the body and dendrites, these are chemically gated channels. A chemical has to bind to open the door. This changes your voltage because if you are next to where that door opened, all that sodium rushes in, your voltage changes. You were negative 70 at rest. if you look at this picture down below, if you're close to where that chemical rushes in, you get a bigger change. Like in a room, if you're close to the air conditioner, you feel really cold. But if you're far across from the room, it may not even feel like the air conditioner is on at all. So we call these graded potentials. Remember graded just means different levels, like this class is graded. Potential is a change in voltage. So if I'm really close to where that chemical is, I'm changed dramatically. dramatically. Like sounds from a TV, the closer you are to the TV or the closer you are to the air conditioner, you feel the sound, you hear the sound or you feel the cold. So right up close to where that sodium is rushing in, I may hit negative 60. If I get a little further away, negative 62. If I get a little further away, negative 66. If I get so far away, it's like the doors aren't even open. Just like I can get so far away from a window unit air conditioner that I don't feel any result. So the point of that is, is different parts of the cell body. and dendrites, within the cell body and dendrites, there may be different voltages. If you're on the side where that acetylcholine has opened the door for sodium, you're going to experience a great voltage change. But if you're all... all the way on the opposite side of the cell body or dendrites, you may not even know those doors are open. The axon is not like that. The axon is all or nothing. The axon are voltage-gated channels. A certain voltage opens the gate. change the little key fob on your car ring to the same voltage that would open every car that has that in Mary Miller. You would go beep beep and like 20 doors would open. That's what's going to happen on the voltage gated channels. It's like dominoes. You know as soon as you you know get one they all fall. So this is not like the previous example or you'd be able to hear your TV from China. Like the signal would never weaken. All of these doors open. Another thing I think of is like at a horse race. when all the horses are like chomping at the bit all the doors open at the same time otherwise it's not fair because some of the horses would lose because their door didn't open right away okay so what I was trying to draw here is is summing this up okay so this is a little neuron I know I'm not an artist and see how I've got that line kind of dividing right at his neck if these guys had a neck so you have the cell body with its doors one two three four or five and then you have the axon with its eight doors. So we have two distinguished parts here. Okay an action potential we saw these with muscles remember a short lasting event we had that diagram with the little peak on it we're gonna have that diagram again. where the membrane potential, which is normally negative 70, rapidly rises and then falls back down. Okay, so on the left there, at the very bottom, it says chemically gated. On the right, it says voltage gated. So remember, we've got chemically gated channels on the cell body, and we have voltage and dendrites, we have voltage gated channels on the axon. Okay, so if you look, the source of the chemical, that little yellow dot, that door's been opened and all this sodium's... rushing in. So that cell used to be negative 70, but now all of that sodium rushed in, so now we're negative 55. But the farther you get away from where that chemical is rushing in, it's like the farther you get away from a window unit air conditioner. It's now negative 57, negative 58. But what we need is, see that blue line that I've drawn with the red arrow? That is what we call threshold. That is where we have to be at negative 60. this is called the axon hillock it's like getting over the hill we have to be at negative 60 at that neck at that hillock in order for the voltage gated channels to open so on the cell body on those chemically gated channels if you don't bring enough sodium in to get to negative 60 remember negative 70 is rest so you need at least 10 a 10 volt change if we don't get to negative 60 those axon doors stay closed. So think of a horse race where the doors don't open. Horses are going to be very frustrated. Okay. We want nerves, neurons to fire. That's their job. We just have to get to negative 60 in order for it to fire. Now, if we're at negative 58, if we're at negative 55, if we're at negative 50, great. If we overshoot it, great. Just like you may have a goal of like money you want to raise for something. If you overshoot it, fan freaking tastic. But if you don't quite get there, it's not good. So say you get to negative 60. at the axon hillock, the doors stay closed. You have to at least get to negative 60. So at negative 60, the voltage gated channels they all open at once, at the exact same time. Nerve signals. This travels really, really fast. They travel at the speed of sound, which you don't need to know that number, but 340 meters per second. Like think of a meter stick. It seems fast to travel a meter stick in a second, let alone 340. And so we're very impressed by that, but then you think how survival is necessary because of this. Because if I touch a hot stove and it took a full minute for that information to get to my brain, my skin will have melted off already. If your deer runs out in front of you and you need to slam on your brakes, if it takes a full minute for that information to get to your brain that there's a deer, the deer is long gone. So we need this to be fast, but still it's impressively fast. Again, the neuron, the axon, fires at negative 60. So it'll fire at negative 59 because you overshot it. It will not fire at 61. So the axon's either going to open or not. You have to get to negative 60. So an action potential... either happens or it doesn't. Just like we had with muscles, it either fires or it doesn't. You either fire a gun or you don't. You either die or you don't. There's no like halfway here. So the axon either sends its signal or it doesn't. So achieving a change of negative 10 is a lot. I mean, that's a lot of sodium rushing in, that's a lot happening, and we need this to happen quickly. So a nerve signal involves multiple neurons. One neuron is just too small to cause this to happen. So we're going to see lots of synapse. Lots of canons. We're seeing this again. Okay, so negative 70 is where we start. Depolarization is all that sodium rushing in. So becoming more positive. Remember, a cell is normally negative. Remember, Number positive 30 is as high up as we can go because at positive 30, all of those potassium channels open. And then we get repolarization. Sometimes we also see hyperpolarization where it gets a little more negative than normal. But the point is, we start at negative 70, all that sodium rushes in, then we get to positive 30, all that potassium leaves, getting us back to normal. Like firing a gun, this is just a quick thing to send the nerve impulse down the line. So... Okay, so what I'm showing here is a synapse, but the little axon end at the top just wouldn't fit in front of the neuron at the bottom. So I was just trying to draw this and make it big enough so we could see what was going on. So at the end of an axon, we see a different kind of door. Instead of sodium being let in, we see voltage-gated calcium channels. So normally, sodium's rushing in, sodium's rushing in. The last door is for calcium. And this calcium coming in is what causes the synaptic vesicles at the end of that axon to release acetylcholine to go across the synaptic cleft to then affect the next neuron. So calcium is the last step to trigger acetylcholine to be released. Then if we look at the bottom picture, acetylcholine opens that door, sodium rushes in. We see negative 55. Remember we were negative 70. Then as long as we're at negative 60 at the axon hillock, the voltage gated doors open. Then at the very end, calcium would come in, triggering more acetylcholine to be released over and over again. So this brings calcium back into the game. Calcium is crucial. The reason why in the skeletal system we had to have the osteoblasts and the osteoclasts doing their thing. We had to have calcitonin and parathyroid hormone doing its thing. Because we said we always have to have enough calcium for our muscles to work and our nerves to fire. So we kind of saw. the calcium come in with the sarcoplasmic reticulum and the troponin tropomyosin and muscles, we now see calcium at the end of the axon is what causes the axon to release its neurotransmitter. Acetylcholine esterase, we see this again. So remember when acetylcholine is released from that vesicle and it opens the receptor, it opens the door on the next neuron, we want to make sure we control it. We don't want our neurons to just fire continuously. just like we didn't want our muscles to contract continuously. So acetylcholine esterase's job is to pull the acetylcholine off there and break it in half, which then you just recycle to make more acetylcholine. So it's just like you're deactivating it, and then you're just going to build it right. So we've got to get to negative 60 to fire. So negative, I just added that to this picture here. Negative 70, the sodium starts coming in. We need enough sodium to get to negative 60, so the axon will fire. If more sodium rushes in, rushes in, fine. We get to that upper limit of positive 30, and then the potassium channels open, so then all those positive ions leave, getting us back to our negativity. So this is showing, I like this picture, it's overwhelming when you first look at it, but it's showing that graph we just did. So see the graph on the right? But they color-coded it. So at rest, we have figure A, where all that sodium's on the outside wanting to get in. Then we have letter B when those doors open. So acetylcholine has opened those doors. All of that sodium is rushing in. The cell is becoming more positive. It peaks then at the very top because now all the potassium, the little purple, dots start to leave. So it kind of shows you what's actually happening in a muscle cell coordinating with diagram. Sometimes we see hyperpolarization, where it gets more negative. It had that little temporary dip. And this goes back to GAB. which all I want you to know about GABA is what's highlighted there remember this is the one neurotransmitter that's inhibitory it puts the brakes on the muscle cells so what he is going to do is inhibit neurons for muscle coordination so we don't just you know fire All of our muscles, he-man, superwoman, we kind of back off a little bit. So how he works, though, is he opens chlorine channels. So a bunch of negativity rushes in, and that's what kind of causes us to temporarily dip below our lungs. So the point is other neurotransmitters can have different effects. Some of them will open doors for K, which allows more K to leave. Some, like acetylcholine, open the doors for sodium to come. So this is just showing the little nerve impulse. An electrical current that travels along dendrites or axons due to ions moving through voltage-gated channels in the neuron's plasma membrane. Voltage-gated channels open and close in response to an electrical voltage, so they are affected by changes in electrical charge around them. When a neuron is at rest, a charge difference is maintained between the inside and outside of the cell. This charge difference is produced and maintained largely by active transport using sodium-potassium pumps. The pumps send sodium ions out of the cell and bring potassium ions in. While other channels allow some flow of potassium ions back out of the cell, the sodium ions cannot easily get back in to replace the lost positive charges. The overall result is that the exterior of the cell has a net positive charge and the interior has a net negative charge. The difference in charge between the interior and exterior of the cell is called the resting membrane potential. A nerve impulse begins when a stimulus disturbs the plasma membrane on a dendrite, causing sodium channels to open. Sodium ions flow into the cell, lessening the charge difference at that location. If the change is enough, it will cause nearby voltage-gated sodium channels to open. This allows so many sodium ions to flood into the cell at that location, that the membrane there is depolarized, with the local region inside the cell having a net positive charge, and the outside of the cell having a net negative charge. This affects neighboring voltage-gated sodium channels which then open, moving the depolarization along the membrane. This moving depolarization is called an action potential. Changes occur behind the action potential to restore the resting membrane potential. The voltage-gated sodium channels close and voltage-gated potassium channels open. This allows a rapid flow of potassium ions out of the cell, repolarizing the membrane so that the inside is again negative and the outside positive. This is followed by use of sodium potassium pumps to fully restore the resting membrane potential and to re-establish proper concentrations of sodium and potassium ions inside and outside the cell. Okay, so that just kind of summed up. I think it's good to have kind of a visual, but you can also go to YouTube, Google nerve impulse, and you'll get tons and tons of videos if that wasn't truly helpful. Okay, so this is showing the benefit of myelin. remember is those big fatty jelly rolls that are caused from either oligodendrocytes in the brain and spinal cord or the Schwann cells in the peripheral nervous system. But it allows the action potentials to leapfrog because if you look where it says one, two, three, four, if you If you had to have action potentials all the way down, it would take a lot longer, especially to get to negative 60. So instead, we can just kind of jump through. So you only have to have action potentials like in those nodes of Ranvir or where there's no fat. So the point is the nerve impulse can kind of leapfrog. It can kind of skip through. And so it covers a lot more territory than if you actually had to fire all the way down that axon. This is a mammal thing. So mammals are the most. advanced animals on the planet right now because our neurons fire so much faster. So lions, tigers, bears, oh my, cats, dogs, bats, rabbits, we have a benefit over like a lizard or a turtle because our neurons can just simply fire faster. So there's two types of nerve impulse conduction, two types of the way to send this signal, saltatory conduction and contiguous. Saltatory is what we just saw with myelin, 50 times faster with myelin, 50 times faster. faster, which is crucial if you're touching a hot stove 50 times is everything. So most of the neurons in your body are myelinated. They're a lot faster. But we have some that we don't need to be Like we said before, some of the really, really small ones, having myelin wouldn't gain us much ground. So we call this contiguous. I remember that because I think of continuous. I think, well, you have to have an action potential all the way down the membrane. You can't leave. leapfrog. But the point is we've got to get to negative 60. We have to have a 10 millivolt change. We've got to get from negative 70 to negative 60 to fire. There's two ways to get there. Temporal summation is when and I just tried to draw it even though I know it's kind of a sad drawing, is when one neuron is stimulating another. So say one neuron is sending a signal. He's sending enough acetylcholine to get enough sodium to rush in to cause a 0.5 change. Well, that's not enough. But what he could do is fire lots of times like a machine gun. So at 0.5, he could fire 20 times and get us to 10. Or you can face a firing squad. Either way, you get the job done. So this is lots of neurons sending their signal. signal at the same time. So we have one, two, three, four neurons stimulating this neuron. And so we call this spatial summation. But in our bodies we use both. Some neurons fire once, others fire rapidly. So imagine you're trying to fill a 50 gallon bucket. You could do it yourself 50 times with one bucket. That would be temporal, like the machine gun. Or you and 49 friends with one gallon. That would be spatial, like the firing squad. Or it's a combination. You can have a firing squad, you can have a firing squad, you can have squad, firing multiple times. Eight friends with one gallon buckets making multiple trips. But the point is we get to 10 change and that's what we wanted. So so far we've just seen acetylcholine as our example of a neurotransmitter. A neurotransmitter is just a chemical. Remember like this little picture shows, we have to have a chemical released because that electricity can't jump through space. It can't jump across the cleft. So we have to have chemicals to do that. So those chemicals are going to stimulate either another neuron or or an effector organ like a muscle or a gland. They can also inhibit as well. So they can say go, go, go, or no, no, no, even though most of the neurotransmitters we focus on say go, go, go. But there's over 30 different types of neurotransmitters, 30 different types of keys produced by the brain and spinal cord. Some neurons produce and release only one, while others release several. So the most typical, acetylcholine, which we've talked about constantly. These stimulate skeletal. muscles. They do this to cause muscle contraction. They also stimulate the digestive system's muscle response, which would be parasympathetic, rest and digest, to rest and repair. Norepinephrine, now we can just call this adrenaline because that's basically what it is. These are released by the postganglionic sympathetic fibers. Don't worry about that, just sympathetic here, autonomic. Sympathetic, fight or flight. heighten your alertness and your mood, your well-being. Helps constrict blood vessels to speed the blood up. Just like if you're trying to water your flowers, like across the way, and you're too lazy to unwind your hose, you can kind of put your thumb over the top and get it to squirt faster. Or you can kink the hose. If you constrict your blood, it speeds it up. So under the effects of adrenaline, you kind of feel like you're paying attention to things. That's why sometimes in a car accident, it only lasts a few seconds, but it feels like it took hours because you were very very alert during that time. Or when you go into a fight, you sort of feel really confident about yourself. And that's the adrenaline. Adrenaline also makes you feel very confident. And that's why sometimes in a good bar fight, when you watch a really tiny dude go after a really big dude, and you know the tiny dude's going to get his ass kicked. But under that adrenaline, he feels really, really confident. Because how cruel in nature would it be to get us to run from a lion, tiger, bear, or my, and we don't have the confidence to feel like we're going to make it. So some other Neurotransmitters, you don't need to know monoamines, unmodified amino acids, and neuropeptides. We're just knowing what these neurotransmitters do. So dopamine is your happy-happy. Serotonin, sleepy, which also affects mood as well. GABA, remember, is the only one inhibitory. So he puts the brakes on muscles. Enkelphins and endorphins, you can lump together. Like I said before, the runner's high. And then substance P was also pain. But this is the one that gets released when you... you eat spicy food. So if you go to Buffalo Wild Wings and do one of their hot wings challenge, it sends a pain sensation to your brain saying this is frigging hot. So your brain releases substance P in response to that. Well, some people like substance P and some people don't. So some people don't like spicy food. Some people do. It's your reaction to this particular neurotransmitter. But drugs have an effect on neuron synaptic impulses, just like like they did on muscles. So some specific drugs that we see. Nicotine. Nicotine is an acetylcholine agonist. Remember, agonists were like master keys. They mimic the action, but there's nothing to shut them off. So they stimulate the nerve because they're agonists. They do the same thing that acetylcholine would normally do. Nicotine stimulates that nerve, but we don't make an enzyme to deactivate nicotine. We make acetylcholine esterase to knock off acetylcholine, but we don't make anything to knock off the nicotine. So this is why... nicotine people enjoy it and why it's addictive there's nothing to knock it off now it will degrade on its own it will break down its own which is why you have to keep smoking and why you crave cigarettes but it also constricts the blood vessels because you're not delivering as much as much oxygen to your body so your blood vessels shrink so if you've ever known smokers or you are a smoker one of the first things you'll notice after you smoke is your hands will feel colder or paler even in color because the blood is kind of pulling back from your your fingers and toes. I've never smoked, but I have a lot of friends that are smokers, and they always talk about their hands being cold. But it gives you a buzz. It turns on that receptor. Otherwise, why would you smoke? Atropine. You may be heard of atropine in the medical field. I just picked it because it's an acetylcholine antagonist. Remember, acetylcholine antagonists were like putting a key in the lock and breaking it. So since it's an antagonist, it can't stimulate the receptor. It can't open that door, but it it blocks the ability of any other neurotransmitters to open that door. Why atropine was developed and why it's so beneficial is doctors give you atropine before surgery to stop your salivary glands. Because if you're in like an eight-hour surgery, you don't want saliva pooling in the back of your throat because then you would choke to death and die, drown in your own saliva. It's kind of like being at the dentist when they use that like, you know, sucking device to like get your salivary from the back of your throat, which is miserable. You wouldn't want a nurse to have to do that through a 12-hour. surgery. What if she gets lazy and forgets? You die. So atropine is very beneficial. If you've ever had major surgery, which luckily I haven't, you wake up and your mouth's incredibly dry, which is why they do those ice chips. Some other drugs that affect neurons. Caffeine, probably the one drug on this list that most of us utilize. Now, caffeine doesn't really change the neurons per se. It makes it more depolarized. So the axon hillock isn't starting at negative 70. It's actually starting at maybe like negative 68 or negative 65. So if caffeine depolarizes the hillock, it makes it easier for us to get to negative 60 to fire. Like normally I have to go from negative 70 to negative 60. But with caffeine, I only have to go from like negative 78 to negative 60. So I only need an 8 change instead of a 10. So it makes the neurons fire faster. Makes them more excited. excitable, which is why caffeine gives us a buzz, gives us a rush. Tetrodotoxin, this is found in certain fish. If you look down below, like the cute little blowfish, how they puff up, those little puffer fish. Some of these fish produce toxins to kind of stun their prey. And what that does is it blocks the voltage gated channels. So those axons can't fire. The neurons won't work. So you can't breathe, your heart stops. So that's how they kind of paralyze and kill their prey. So Tetrodotoxin is also called the voodoo medicine because voodoo priestesses used to take this to convince people like they were in the beyond in the other world because it'll slow your breathing and your heart rate down so much that actually like a coroner will pronounce you dead. It's rumored that a lot of mob bosses did this as well to like fake their own death. Of course, it's a pretty big risk because you may take too much of this toxin and actually die because it does lower your breathing and heart rate so much. This is also why like to eat blowfish like... like sushi, you have to get a chef that knows how to prepare it, because otherwise you can die. And so this is kind of like a test of manliness in Japan, to eat this particular sushi that could kill you, which I like food, but I don't think it's worth it. worth that, you know. But I had a student once who had tried this and he said it did make his mouth numb, which I think is creepy. But some people die from eating sushi that was not prepared correctly from these fish that have this toxin. But again, it's like a test of manhood sometimes is to see this, to eat this fish and see if you die. Crazy. And then cocaine. Cocaine blocks dopamine reuptake. So dopamine, remember, is your happy. happy chemical. Normally, just like acetylcholine gets released, opens the door, and then breaks down, normally dopamine does that as well. But cocaine stops you from reabsorbing the dopamine so it stays in that synaptic cleft longer. It keeps your happy doors, your pleasure response, open. The problem is our body adjusts very quickly. So your body says, okay, well, the happy switches you have are staying on longer for whatever reason. You don't need as many of them. them. So every time you do cocaine, you have to have more and more of it to achieve that same high because your body starts making less and less doors for those cocaine keys to open. So this is really how we achieve kind of tolerance to drugs is because our brain adapts. But our brain loves drugs. Our brain loves to be stimulated. I mean, it's just like when you were a little kid and you spun around in circles till you fell down. We like altering our brain chemistry. If you take a monkey and put them in a cage where they have two buttons, and one button will give them all the food they want, and one button will give them all the cocaine they want, they will die because they'll never hit the food button. They'll just keep acting. asking for more cocaine. So a lot of other animals, they seek this ability to change their brain chemistry. You can go on YouTube and watch videos of monkeys getting drunk because they'll find fruit out in nature that started fermenting, that started rotting. And they learn that if they eat it, it gives them a buzz. Same thing with horses. Horses do this. Most animals will seek that natural high. So we're no different than that.

Okay, neurons are similar to muscle cells in the sense that they're going to be able to send an impulse. They're able to communicate. They are excitable tissues.

So we're going to see the cell membrane again. So to review, remember the inside of a normal cell is negative. reasons why.

The sodium potassium pump. For every two positive that you bring in, you have to give up three positive. So that's like getting two dollars, but you have to give up three.

Puts you at a negative. Cell membranes always have a small potassium leak, so there's a lot of potential for a small potassium leak. there are doors that are always open from the inside out to lose potassium.

Just like I said, you may have a crack under your door where you lose a lot of air conditioning or lights able to get through. So we always lose positive K, therefore that's at a negative. And all the junk inside the cells, all the organelles, the DNA and RNA, the proteins, everything else, negative. So this results in a negative normal inside. But this is good because we want to create a reason, remember, for sodium to want to come in.

Yeah. As soon as those doors open, because of acetylcholine opening the door, the neurotransmitter being the key, sodium wants in because there's lots of sodium outside the cell, and diffusion always tells us we want to go from where we're crowded to where we're not, and opposites attract. All that sodium wants to be with all that negativity.

So we call this the electrochemical gradient. So this is a review for muscles. Chemical and electrical factors determine where ions want to go. So diffusion being chemical, the electrical being opposite. it's a tract.

So remember, negative 70 is the number that I want you to know. So neurons are negative 70 at rest. Millivolts, one one-thousandth of a volt.

So anytime you see that little negative sign, that's referring to the inside of the cell. So we saw this with muscles. Okay, so where things get kind of new.

This little drawing here is on a body, the cell body, or on the dendrites. So on the cell body and dendrites, we have what are called chemically gated channels. And that's what we're going to call them.

Technically they also call them ligand gated channels, but ligand just means chemical. So chemically gated channels. So we're going to see two different kinds of doors, chemically gated and voltage gated. So on the cell body and dendrite are chemically gated channels.

The right chemical opens the door. So we've already seen these with acetylcholine. So these are acetylcholine sits there like a key and opens the door so a chemically gated channel So this happens on the cell body and on the dendrites on the axon though Which again is what I was just trying to draw there on the axon on are voltage-gated channels.

And these are like those little key fobs that a lot of people have on their cars where they click that and it goes beep, beep, and it opens the door. You didn't have a physical key opening the door, the right voltage opened the door. So, On the dendrites and cell bodies, you have chemically gated channels, where a neurotransmitter has to physically open the door.

On the axon, voltage gated. Now, we're going to see they open at negative 60. So that's another number we need to know. So a cell is negative 70 at rest, and these axon gates open at negative 60. So if I am negative 70 in my checking account, and I need to get to negative 60, I need 10 bucks.

So we need enough sodium. sodium is positive. We need enough sodium to rush in to get us a 10 change to get these gates to open.

So chemically gated versus voltage gated. So on the body and dendrites, these are chemically gated channels. A chemical has to bind to open the door. This changes your voltage because if you are next to where that door opened, all that sodium rushes in, your voltage changes. You were negative 70 at rest.

if you look at this picture down below, if you're close to where that chemical rushes in, you get a bigger change. Like in a room, if you're close to the air conditioner, you feel really cold. But if you're far across from the room, it may not even feel like the air conditioner is on at all.

So we call these graded potentials. Remember graded just means different levels, like this class is graded. Potential is a change in voltage.

So if I'm really close to where that chemical is, I'm changed dramatically. dramatically. Like sounds from a TV, the closer you are to the TV or the closer you are to the air conditioner, you feel the sound, you hear the sound or you feel the cold.

So right up close to where that sodium is rushing in, I may hit negative 60. If I get a little further away, negative 62. If I get a little further away, negative 66. If I get so far away, it's like the doors aren't even open. Just like I can get so far away from a window unit air conditioner that I don't feel any result. So the point of that is, is different parts of the cell body.

and dendrites, within the cell body and dendrites, there may be different voltages. If you're on the side where that acetylcholine has opened the door for sodium, you're going to experience a great voltage change. But if you're all... all the way on the opposite side of the cell body or dendrites, you may not even know those doors are open. The axon is not like that.

The axon is all or nothing. The axon are voltage-gated channels. A certain voltage opens the gate.

change the little key fob on your car ring to the same voltage that would open every car that has that in Mary Miller. You would go beep beep and like 20 doors would open. That's what's going to happen on the voltage gated channels. It's like dominoes.

You know as soon as you you know get one they all fall. So this is not like the previous example or you'd be able to hear your TV from China. Like the signal would never weaken. All of these doors open.

Another thing I think of is like at a horse race. when all the horses are like chomping at the bit all the doors open at the same time otherwise it's not fair because some of the horses would lose because their door didn't open right away okay so what I was trying to draw here is is summing this up okay so this is a little neuron I know I'm not an artist and see how I've got that line kind of dividing right at his neck if these guys had a neck so you have the cell body with its doors one two three four or five and then you have the axon with its eight doors. So we have two distinguished parts here.

Okay an action potential we saw these with muscles remember a short lasting event we had that diagram with the little peak on it we're gonna have that diagram again. where the membrane potential, which is normally negative 70, rapidly rises and then falls back down. Okay, so on the left there, at the very bottom, it says chemically gated.

On the right, it says voltage gated. So remember, we've got chemically gated channels on the cell body, and we have voltage and dendrites, we have voltage gated channels on the axon. Okay, so if you look, the source of the chemical, that little yellow dot, that door's been opened and all this sodium's...

rushing in. So that cell used to be negative 70, but now all of that sodium rushed in, so now we're negative 55. But the farther you get away from where that chemical is rushing in, it's like the farther you get away from a window unit air conditioner. It's now negative 57, negative 58. But what we need is, see that blue line that I've drawn with the red arrow?

That is what we call threshold. That is where we have to be at negative 60. this is called the axon hillock it's like getting over the hill we have to be at negative 60 at that neck at that hillock in order for the voltage gated channels to open so on the cell body on those chemically gated channels if you don't bring enough sodium in to get to negative 60 remember negative 70 is rest so you need at least 10 a 10 volt change if we don't get to negative 60 those axon doors stay closed. So think of a horse race where the doors don't open.

Horses are going to be very frustrated. Okay. We want nerves, neurons to fire. That's their job. We just have to get to negative 60 in order for it to fire.

Now, if we're at negative 58, if we're at negative 55, if we're at negative 50, great. If we overshoot it, great. Just like you may have a goal of like money you want to raise for something. If you overshoot it, fan freaking tastic. But if you don't quite get there, it's not good.

So say you get to negative 60. at the axon hillock, the doors stay closed. You have to at least get to negative 60. So at negative 60, the voltage gated channels they all open at once, at the exact same time. Nerve signals. This travels really, really fast. They travel at the speed of sound, which you don't need to know that number, but 340 meters per second.

Like think of a meter stick. It seems fast to travel a meter stick in a second, let alone 340. And so we're very impressed by that, but then you think how survival is necessary because of this. Because if I touch a hot stove and it took a full minute for that information to get to my brain, my skin will have melted off already. If your deer runs out in front of you and you need to slam on your brakes, if it takes a full minute for that information to get to your brain that there's a deer, the deer is long gone.

So we need this to be fast, but still it's impressively fast. Again, the neuron, the axon, fires at negative 60. So it'll fire at negative 59 because you overshot it. It will not fire at 61. So the axon's either going to open or not.

You have to get to negative 60. So an action potential... either happens or it doesn't. Just like we had with muscles, it either fires or it doesn't. You either fire a gun or you don't.

You either die or you don't. There's no like halfway here. So the axon either sends its signal or it doesn't. So achieving a change of negative 10 is a lot.

I mean, that's a lot of sodium rushing in, that's a lot happening, and we need this to happen quickly. So a nerve signal involves multiple neurons. One neuron is just too small to cause this to happen. So we're going to see lots of synapse.

Lots of canons. We're seeing this again. Okay, so negative 70 is where we start.

Depolarization is all that sodium rushing in. So becoming more positive. Remember, a cell is normally negative. Remember, Number positive 30 is as high up as we can go because at positive 30, all of those potassium channels open. And then we get repolarization.

Sometimes we also see hyperpolarization where it gets a little more negative than normal. But the point is, we start at negative 70, all that sodium rushes in, then we get to positive 30, all that potassium leaves, getting us back to normal. Like firing a gun, this is just a quick thing to send the nerve impulse down the line.

So... Okay, so what I'm showing here is a synapse, but the little axon end at the top just wouldn't fit in front of the neuron at the bottom. So I was just trying to draw this and make it big enough so we could see what was going on. So at the end of an axon, we see a different kind of door. Instead of sodium being let in, we see voltage-gated calcium channels.

So normally, sodium's rushing in, sodium's rushing in. The last door is for calcium. And this calcium coming in is what causes the synaptic vesicles at the end of that axon to release acetylcholine to go across the synaptic cleft to then affect the next neuron. So calcium is the last step to trigger acetylcholine to be released.

Then if we look at the bottom picture, acetylcholine opens that door, sodium rushes in. We see negative 55. Remember we were negative 70. Then as long as we're at negative 60 at the axon hillock, the voltage gated doors open. Then at the very end, calcium would come in, triggering more acetylcholine to be released over and over again. So this brings calcium back into the game.

Calcium is crucial. The reason why in the skeletal system we had to have the osteoblasts and the osteoclasts doing their thing. We had to have calcitonin and parathyroid hormone doing its thing.

Because we said we always have to have enough calcium for our muscles to work and our nerves to fire. So we kind of saw. the calcium come in with the sarcoplasmic reticulum and the troponin tropomyosin and muscles, we now see calcium at the end of the axon is what causes the axon to release its neurotransmitter. Acetylcholine esterase, we see this again. So remember when acetylcholine is released from that vesicle and it opens the receptor, it opens the door on the next neuron, we want to make sure we control it.

We don't want our neurons to just fire continuously. just like we didn't want our muscles to contract continuously. So acetylcholine esterase's job is to pull the acetylcholine off there and break it in half, which then you just recycle to make more acetylcholine. So it's just like you're deactivating it, and then you're just going to build it right. So we've got to get to negative 60 to fire.

So negative, I just added that to this picture here. Negative 70, the sodium starts coming in. We need enough sodium to get to negative 60, so the axon will fire. If more sodium rushes in, rushes in, fine. We get to that upper limit of positive 30, and then the potassium channels open, so then all those positive ions leave, getting us back to our negativity.

So this is showing, I like this picture, it's overwhelming when you first look at it, but it's showing that graph we just did. So see the graph on the right? But they color-coded it.

So at rest, we have figure A, where all that sodium's on the outside wanting to get in. Then we have letter B when those doors open. So acetylcholine has opened those doors.

All of that sodium is rushing in. The cell is becoming more positive. It peaks then at the very top because now all the potassium, the little purple, dots start to leave. So it kind of shows you what's actually happening in a muscle cell coordinating with diagram. Sometimes we see hyperpolarization, where it gets more negative.

It had that little temporary dip. And this goes back to GAB. which all I want you to know about GABA is what's highlighted there remember this is the one neurotransmitter that's inhibitory it puts the brakes on the muscle cells so what he is going to do is inhibit neurons for muscle coordination so we don't just you know fire All of our muscles, he-man, superwoman, we kind of back off a little bit.

So how he works, though, is he opens chlorine channels. So a bunch of negativity rushes in, and that's what kind of causes us to temporarily dip below our lungs. So the point is other neurotransmitters can have different effects. Some of them will open doors for K, which allows more K to leave.

Some, like acetylcholine, open the doors for sodium to come. So this is just showing the little nerve impulse. An electrical current that travels along dendrites or axons due to ions moving through voltage-gated channels in the neuron's plasma membrane.

Voltage-gated channels open and close in response to an electrical voltage, so they are affected by changes in electrical charge around them. When a neuron is at rest, a charge difference is maintained between the inside and outside of the cell. This charge difference is produced and maintained largely by active transport using sodium-potassium pumps. The pumps send sodium ions out of the cell and bring potassium ions in. While other channels allow some flow of potassium ions back out of the cell, the sodium ions cannot easily get back in to replace the lost positive charges.

The overall result is that the exterior of the cell has a net positive charge and the interior has a net negative charge. The difference in charge between the interior and exterior of the cell is called the resting membrane potential. A nerve impulse begins when a stimulus disturbs the plasma membrane on a dendrite, causing sodium channels to open.

Sodium ions flow into the cell, lessening the charge difference at that location. If the change is enough, it will cause nearby voltage-gated sodium channels to open. This allows so many sodium ions to flood into the cell at that location, that the membrane there is depolarized, with the local region inside the cell having a net positive charge, and the outside of the cell having a net negative charge.

This affects neighboring voltage-gated sodium channels which then open, moving the depolarization along the membrane. This moving depolarization is called an action potential. Changes occur behind the action potential to restore the resting membrane potential. The voltage-gated sodium channels close and voltage-gated potassium channels open.

This allows a rapid flow of potassium ions out of the cell, repolarizing the membrane so that the inside is again negative and the outside positive. This is followed by use of sodium potassium pumps to fully restore the resting membrane potential and to re-establish proper concentrations of sodium and potassium ions inside and outside the cell. Okay, so that just kind of summed up. I think it's good to have kind of a visual, but you can also go to YouTube, Google nerve impulse, and you'll get tons and tons of videos if that wasn't truly helpful.

Okay, so this is showing the benefit of myelin. remember is those big fatty jelly rolls that are caused from either oligodendrocytes in the brain and spinal cord or the Schwann cells in the peripheral nervous system. But it allows the action potentials to leapfrog because if you look where it says one, two, three, four, if you If you had to have action potentials all the way down, it would take a lot longer, especially to get to negative 60. So instead, we can just kind of jump through.

So you only have to have action potentials like in those nodes of Ranvir or where there's no fat. So the point is the nerve impulse can kind of leapfrog. It can kind of skip through. And so it covers a lot more territory than if you actually had to fire all the way down that axon.

This is a mammal thing. So mammals are the most. advanced animals on the planet right now because our neurons fire so much faster.

So lions, tigers, bears, oh my, cats, dogs, bats, rabbits, we have a benefit over like a lizard or a turtle because our neurons can just simply fire faster. So there's two types of nerve impulse conduction, two types of the way to send this signal, saltatory conduction and contiguous. Saltatory is what we just saw with myelin, 50 times faster with myelin, 50 times faster. faster, which is crucial if you're touching a hot stove 50 times is everything.

So most of the neurons in your body are myelinated. They're a lot faster. But we have some that we don't need to be Like we said before, some of the really, really small ones, having myelin wouldn't gain us much ground. So we call this contiguous. I remember that because I think of continuous.

I think, well, you have to have an action potential all the way down the membrane. You can't leave. leapfrog. But the point is we've got to get to negative 60. We have to have a 10 millivolt change.

We've got to get from negative 70 to negative 60 to fire. There's two ways to get there. Temporal summation is when and I just tried to draw it even though I know it's kind of a sad drawing, is when one neuron is stimulating another. So say one neuron is sending a signal. He's sending enough acetylcholine to get enough sodium to rush in to cause a 0.5 change.

Well, that's not enough. But what he could do is fire lots of times like a machine gun. So at 0.5, he could fire 20 times and get us to 10. Or you can face a firing squad.

Either way, you get the job done. So this is lots of neurons sending their signal. signal at the same time. So we have one, two, three, four neurons stimulating this neuron.

And so we call this spatial summation. But in our bodies we use both. Some neurons fire once, others fire rapidly. So imagine you're trying to fill a 50 gallon bucket.

You could do it yourself 50 times with one bucket. That would be temporal, like the machine gun. Or you and 49 friends with one gallon. That would be spatial, like the firing squad.

Or it's a combination. You can have a firing squad, you can have a firing squad, you can have squad, firing multiple times. Eight friends with one gallon buckets making multiple trips. But the point is we get to 10 change and that's what we wanted.

So so far we've just seen acetylcholine as our example of a neurotransmitter. A neurotransmitter is just a chemical. Remember like this little picture shows, we have to have a chemical released because that electricity can't jump through space.

It can't jump across the cleft. So we have to have chemicals to do that. So those chemicals are going to stimulate either another neuron or or an effector organ like a muscle or a gland.

They can also inhibit as well. So they can say go, go, go, or no, no, no, even though most of the neurotransmitters we focus on say go, go, go. But there's over 30 different types of neurotransmitters, 30 different types of keys produced by the brain and spinal cord.

Some neurons produce and release only one, while others release several. So the most typical, acetylcholine, which we've talked about constantly. These stimulate skeletal. muscles. They do this to cause muscle contraction.

They also stimulate the digestive system's muscle response, which would be parasympathetic, rest and digest, to rest and repair. Norepinephrine, now we can just call this adrenaline because that's basically what it is. These are released by the postganglionic sympathetic fibers.

Don't worry about that, just sympathetic here, autonomic. Sympathetic, fight or flight. heighten your alertness and your mood, your well-being.

Helps constrict blood vessels to speed the blood up. Just like if you're trying to water your flowers, like across the way, and you're too lazy to unwind your hose, you can kind of put your thumb over the top and get it to squirt faster. Or you can kink the hose. If you constrict your blood, it speeds it up.

So under the effects of adrenaline, you kind of feel like you're paying attention to things. That's why sometimes in a car accident, it only lasts a few seconds, but it feels like it took hours because you were very very alert during that time. Or when you go into a fight, you sort of feel really confident about yourself.

And that's the adrenaline. Adrenaline also makes you feel very confident. And that's why sometimes in a good bar fight, when you watch a really tiny dude go after a really big dude, and you know the tiny dude's going to get his ass kicked. But under that adrenaline, he feels really, really confident.

Because how cruel in nature would it be to get us to run from a lion, tiger, bear, or my, and we don't have the confidence to feel like we're going to make it. So some other Neurotransmitters, you don't need to know monoamines, unmodified amino acids, and neuropeptides. We're just knowing what these neurotransmitters do. So dopamine is your happy-happy.

Serotonin, sleepy, which also affects mood as well. GABA, remember, is the only one inhibitory. So he puts the brakes on muscles.

Enkelphins and endorphins, you can lump together. Like I said before, the runner's high. And then substance P was also pain.

But this is the one that gets released when you... you eat spicy food. So if you go to Buffalo Wild Wings and do one of their hot wings challenge, it sends a pain sensation to your brain saying this is frigging hot.

So your brain releases substance P in response to that. Well, some people like substance P and some people don't. So some people don't like spicy food. Some people do.

It's your reaction to this particular neurotransmitter. But drugs have an effect on neuron synaptic impulses, just like like they did on muscles. So some specific drugs that we see. Nicotine.

Nicotine is an acetylcholine agonist. Remember, agonists were like master keys. They mimic the action, but there's nothing to shut them off.

So they stimulate the nerve because they're agonists. They do the same thing that acetylcholine would normally do. Nicotine stimulates that nerve, but we don't make an enzyme to deactivate nicotine. We make acetylcholine esterase to knock off acetylcholine, but we don't make anything to knock off the nicotine. So this is why...

nicotine people enjoy it and why it's addictive there's nothing to knock it off now it will degrade on its own it will break down its own which is why you have to keep smoking and why you crave cigarettes but it also constricts the blood vessels because you're not delivering as much as much oxygen to your body so your blood vessels shrink so if you've ever known smokers or you are a smoker one of the first things you'll notice after you smoke is your hands will feel colder or paler even in color because the blood is kind of pulling back from your your fingers and toes. I've never smoked, but I have a lot of friends that are smokers, and they always talk about their hands being cold. But it gives you a buzz. It turns on that receptor. Otherwise, why would you smoke?

Atropine. You may be heard of atropine in the medical field. I just picked it because it's an acetylcholine antagonist. Remember, acetylcholine antagonists were like putting a key in the lock and breaking it.

So since it's an antagonist, it can't stimulate the receptor. It can't open that door, but it it blocks the ability of any other neurotransmitters to open that door. Why atropine was developed and why it's so beneficial is doctors give you atropine before surgery to stop your salivary glands. Because if you're in like an eight-hour surgery, you don't want saliva pooling in the back of your throat because then you would choke to death and die, drown in your own saliva.

It's kind of like being at the dentist when they use that like, you know, sucking device to like get your salivary from the back of your throat, which is miserable. You wouldn't want a nurse to have to do that through a 12-hour. surgery.

What if she gets lazy and forgets? You die. So atropine is very beneficial.

If you've ever had major surgery, which luckily I haven't, you wake up and your mouth's incredibly dry, which is why they do those ice chips. Some other drugs that affect neurons. Caffeine, probably the one drug on this list that most of us utilize.

Now, caffeine doesn't really change the neurons per se. It makes it more depolarized. So the axon hillock isn't starting at negative 70. It's actually starting at maybe like negative 68 or negative 65. So if caffeine depolarizes the hillock, it makes it easier for us to get to negative 60 to fire. Like normally I have to go from negative 70 to negative 60. But with caffeine, I only have to go from like negative 78 to negative 60. So I only need an 8 change instead of a 10. So it makes the neurons fire faster.

Makes them more excited. excitable, which is why caffeine gives us a buzz, gives us a rush. Tetrodotoxin, this is found in certain fish. If you look down below, like the cute little blowfish, how they puff up, those little puffer fish. Some of these fish produce toxins to kind of stun their prey.

And what that does is it blocks the voltage gated channels. So those axons can't fire. The neurons won't work. So you can't breathe, your heart stops.

So that's how they kind of paralyze and kill their prey. So Tetrodotoxin is also called the voodoo medicine because voodoo priestesses used to take this to convince people like they were in the beyond in the other world because it'll slow your breathing and your heart rate down so much that actually like a coroner will pronounce you dead. It's rumored that a lot of mob bosses did this as well to like fake their own death. Of course, it's a pretty big risk because you may take too much of this toxin and actually die because it does lower your breathing and heart rate so much.

This is also why like to eat blowfish like... like sushi, you have to get a chef that knows how to prepare it, because otherwise you can die. And so this is kind of like a test of manliness in Japan, to eat this particular sushi that could kill you, which I like food, but I don't think it's worth it. worth that, you know.

But I had a student once who had tried this and he said it did make his mouth numb, which I think is creepy. But some people die from eating sushi that was not prepared correctly from these fish that have this toxin. But again, it's like a test of manhood sometimes is to see this, to eat this fish and see if you die.

Crazy. And then cocaine. Cocaine blocks dopamine reuptake.

So dopamine, remember, is your happy. happy chemical. Normally, just like acetylcholine gets released, opens the door, and then breaks down, normally dopamine does that as well.

But cocaine stops you from reabsorbing the dopamine so it stays in that synaptic cleft longer. It keeps your happy doors, your pleasure response, open. The problem is our body adjusts very quickly.

So your body says, okay, well, the happy switches you have are staying on longer for whatever reason. You don't need as many of them. them. So every time you do cocaine, you have to have more and more of it to achieve that same high because your body starts making less and less doors for those cocaine keys to open.

So this is really how we achieve kind of tolerance to drugs is because our brain adapts. But our brain loves drugs. Our brain loves to be stimulated.

I mean, it's just like when you were a little kid and you spun around in circles till you fell down. We like altering our brain chemistry. If you take a monkey and put them in a cage where they have two buttons, and one button will give them all the food they want, and one button will give them all the cocaine they want, they will die because they'll never hit the food button. They'll just keep acting. asking for more cocaine.

So a lot of other animals, they seek this ability to change their brain chemistry. You can go on YouTube and watch videos of monkeys getting drunk because they'll find fruit out in nature that started fermenting, that started rotting. And they learn that if they eat it, it gives them a buzz. Same thing with horses.

Horses do this. Most animals will seek that natural high. So we're no different than that.

Transcript for:Understanding Neuron Function and Signaling

Transcript for:
Understanding Neuron Function and Signaling