all right so we're talking about the functions of the autonomic nervous system and then eventually we're going to talk about why things happen the way they do with certain neurotransmitters and chemicals and the role the receptor and specifically how the receptor triggers the change in the cellular Behavior which then does and makes the change that we want to do to maintain homeostasis all right so and we talk about sympathetic function you probably know that this is our fight or flight system it's if you look at the evolution of the brain it's one of the oldest parts of the brain uh or that nuclei which are controlling these are one of the oldest part of the brain and it's about you either stick around to preserve your life as an organism because the ultimate goal of an organism is to reproduce and pass on its genes you stick around and fight for your life or you run away to protect it essentially what it is and so sympathetic we will see that being um activated in um I guess we could say stressful situations and this is controlled in two ways so you have the nervous system meaning neurons specifically the US of the sympathetic so we have neurons and these neurons are going to release norepinephrine on The receptors so when you think sympathetic you need to think norepinephrine being released from those neurons but the endocrine system is also involved in this specifically the Adrenal medulla and that's going to release epinephrine which is very similar in structure to norepinephrine it's a monoamine it binds to a lot of the same receptors not all the same but a lot of the same so about 75 percent of the secretions from the Adrenal medulla into the bladder epinephrine about 25 percent are norepinephrine so the fight or flight is going to be activated by both because what we have and you should have reviewed this or should have seen it when you reviewed nine two is that there are neurons that are part of the sympathetic that connect to the Adrenal medulla now remember in the autonomic pathway there's two neurons there's the preganglionic and there's the postganglionic neuron always two neurons in an autonomic pathway when I say autonomic you need to automatically think motor involuntary motor I don't care if we're talking sympathetic repair sympathetic there's always two neurons in that pathway and those neurons will synapse if we just look at a single pathway those neurons will synapse at an autonomic ganglion now remember ganglion is a collection of nerve cell bodies in the peripheral nervous system nucleus is a collection of nerve cell bodies in the central nervous system now if we look at this sympathetic all these effectors are going to be cardiac muscle smooth muscle or glands so digestive glands and the other endocrine glands and so on if we look at the pathway to the Adrenal medulla we have a neuron and these are come from the spinal cord we have a preganglionic neuron that synapses with all the individual cells in the Adrenal medulla so here's your adrenal glands it's on the superior poles of the kidneys there's two parts there's the inner part and the outer part each of these cells in the Adrenal medulla is a postganglionic cell in a sense these cells of the Adrenal medulla are neurons that do not have axons and so when this acetylcholine is released from this neuron onto these cells they're going to secrete epinephrine and norepinephrine into the blood so when you have an activated fight or flight you will have all of these activated and that's what's I guess unique about the sympathetic is it's very broad widespread acting is that when it's activated it activates everything that could possibly have sympathetic innervation whereas the parasympathetic is very localized and you can have very specific and find control of your parasympathetic things that are under parasympathetic control and this has to do with the Divergence of these postganglionic cells so there could be many many postganglionic cells that synapse with a single preganglionic so um I want to talk briefly about something called autonomic tone thank you this simply refers to the continuous firing of neurons in the background that these neurons are always sending signals to their effector so the continuous firing of autonomic neurons which then in turn um I don't want to say affect the effector but that's what they're doing is they're causing the effector to do something and we can have both sympathetic and parasympathetic tone I'll talk about parasympathetic tone in a minute let's look at a sympathetic tone so what this means is that there's a constant firing and sending a sympathetic stimuli down these sympathetic pathways which tells these effectors skeletal muscle cardiac muscle smooth muscle or glands to keep doing something which means that if we and let me look let me dry this here so if this represents and this represents the number of signals in a specific unit of time we're gonna get effect I'll just say 1X bear with me if we increase the sympathetic stimulation the constant background firing and we have more signals in a specific unit of time that means we're gonna in a way see more activation of that effector it's going to do more if we slow down that sympathetic firing then we have less Action potentials in a unit of time then that will slow down whatever that cell does and a really good example of this is what happens in your blood vessels of your arteries arterials is that in order to maintain a certain diameter is that we are constantly sending parasympathetic signals to the smooth muscles in those arterioles and when those smooth muscles are stimulated they will contract and in order to maintain a certain level of contraction which keeps your blood vessels at a certain diameter we have to send a certain amount of stimuli so if the diameter of the blood vessel at a stimulation of 1x is this and we increase the number of signals going to those smooth muscle cells that is going to cause those smooth muscle cells to contract and the diameter of that vessel is going to shrink the same time if we send less signals to the smooth muscle in those vessels then that vessel will dilate because those cells are relaxing and they're not Contracting as often and so the vest the diameter of your blood vessel will be bigger this is important because sometimes certain tissues and cells are only innovated by one of these branches so like the blood vessels are only innervated by the sympathetic nervous system so the only way we can get those smooth muscles to relax and cause vasodilation is to decrease the amount of stimuli going to those smooth muscle cells okay that's what autonomic tone is we have it in parasympathetic as well and that's to keep your heart rate less than 100 beats a minute at rest uh let me call your attention too where is it so in your packet uh find page 216. and I will give you all these tables so I'm going to give you what's on page 213 on the test I'm gonna go over that today uh I give you page 214 on the test and I give you page 216 on the test you don't have to memorize it you got to understand what it's telling you so page 216 is telling you where we have this tone this autonomic tone and background firing so you can see the second one down arterials predominant tone is sympathetic meaning that we are constantly sending sympathetic signals to those smooth muscle cells of the arterioles and if we lose that tone if for some reason the sympathetic stops firing that means those smooth muscle cells are going to relax and when your blood vessels dilate and you get a lot bigger in diameter your blood pressure drops hence uh the what's the effect of the loss of that sympathetic tone hypotension low blood pressure now we're going to come back and talk about this in unit four I am going to talk today about these alpha-1 adrenergic acceptor receptors to hopefully help you understand why what happens when we stimulate those why we see smooth muscle contraction happening and causing that vasodilation you can also see that there's parasympathetic tone that the heart is constantly receiving stimulation from the vagus nerve at rest which keeps your heart rate low 100 beats a minute and if something were to happen and you were to lose that vagal tone it's called your heart rate would go up so the vagus nerve acts as a break on the heart to keep the heart rate lower again something we address in more detail uh in unit four and we'll look at the physiology of the SA node and why this the parasympathetic causes the heart rate to decrease anyway you'll probably see a question or two about tone on the exam and you may have to refer to this chart okay I will give you page 216 to 14 and 213. you don't have to memorize those you have to understand how to read them but I will give you those what's on 215 is basically the same as what's on 214 just broken down a little differently so you can ignore 250 215 if you want it's pretty much the same I think 214 is a little bit more um concise and you don't even really need to memorize what the sympathetic and parasympathetic do because it's on the chart and if you know how to read the chart you can probably yes or determine the sympathetic or parasympathetic effect okay all right so we'll come back to page 213 shortly all right let's quickly look at the parasympathetic this is what we call our resting and digesting this is predominantly active while at rest not in a fight or flight situation parasympathetic again two neurons in the pathway synapse in the ganglion what neurotransmitters are always released from the first neuron in the autonomic pathway acetylcholine I think I addressed this last time and what type of receptor is found on the dendrites and cell body of that postganglionic cell the second cell in an autonomic pathway it's the receptor that binds to acetylcholine that ensures an action potential will happen in that cell but you know well the res the receptor is a nicotinic receptor and I'm going to come back and review these it's a nicotinic receptor but it's a ligand nicotinic receptors are always ligandated meaning that when acetylcholine binds to them it actually opens a channel let's sodium in potassium out and that's what triggers that postsynaptic potential that's going to put that second neuron over threshold so regardless if it's sympathetic or parasympathetic that first neuron will always release acetylcholine and it will always bind to nicotinic receptors on that second cell have to make sure you understand that where some of the differences come in is what's released from that second cell we said sympathetic it's going to release norepinephrine now there's a couple of exceptions which I will just not get into your sweat I'll mention it your sweat glands actually are only innervated by the sympathetic but those neurons actually release acetylcholine even though it's sympathetic for whatever reason those releases acetylcholine it will not be on the test okay don't worry about it if we're talking parasympathetic then and let's say this is this is the heart okay these are going to be uh this also releases acetylcholine so parasympathetic always releases acetylcholine from the second neuron and The receptors are what we call muscarinic I'll talk about those today we're going to look at M2 and M3 what were the types of receptors that the uh found associated with sympathetic ready remember that I think I addressed that when we were talking about section seven five last time Alpha and beta okay we're gonna go over this again it's the alpha and beta receptors are what what we find on the effectors over here if this is a sympathetic pathway so this release is norepinephrine and these receptors are either going to be alpha or beta and we're going to look at that we're going to look at what happens when an alpha receptor is stimulated what happens inside the cell and why do we get smooth muscle contraction of the blood vessels and that's the kind of stuff that's related to section or on page 213. I'll go over that chart with you too okay uh you don't really need to know this again this is a kind of a duplicate of those tables on page 214 and 215 but it tells you the different receptor types and um I can't read this because I bring my glasses again today it breaks it down by sympathetic and parasympathetic all right so let's let's I guess I kind of talked about some of this already so let's talk about acetylcholine real quick so cholinergic is going to refer to acetylcholine so we already mentioned the nicotinic receptors I guess I forgot this slide was here we'll just write it again so The nicotinic receptors remember these are ligand-gated they're going to allow sodium in potassium out and this is what's called produces that postsynaptic potential which then leads to the action potential in the postganglionic cell so there's our first neuron and the autonomic pathway this is always acetylcholine and these receptors on the second neuron in any autonomic pathway as I said these are always nicotinic receptors they're excitatory they create excitatory postsynaptic potentials increasing the likelihood of an action potential in that second cell which is what we want and if an action potential happens in cell 2 that means that this second cell is going to be able to release its epinephrine or acetyl or norepinephrine acetylcholine depending if it's sympathetic or parasympathetic now the other place are the other types of receptors as I mentioned are The muscarinic receptors these are only associated with one exception uh with the parasympathetic effectors so any of the cardiac muscle smooth muscle or glands that are activated when we want the parasympathetic to do its job those are always going to be muscarinic receptors we have M2 and M3 as I just previously mentioned and what we'll find is that some of these the m2s are actually what we call inhibitory they actually inhibit the effector or change the behavior of the effector to kind of slow something down whereas the M3 are going to be what we call excitatory and they actually increase the behavior or excited excitability or you know cause something more to happen yeah so so when we look at the fact that sympathetic always releases norepinephrine there is an exception to that and the neurons that innervate your sweat glands which are only sympathetic they actually release acetylcholine which means that the receptors on those are going to be muscarinic I'm not going to ask you that we're just going to go with sympathetic norepinephrine parasympathetic acetylcholine okay maybe later on you'll have to learn something about that but right now we're just going to try and eliminate one of those accept this accept that all right so let's look at adrenergic then so when I say adrenergic I'm talking about norepinephrine epinephrine as the chemical that's going to bind to the effector so you can always think sympathetic when you hear the term adrenergic so sympathetic effects and we know that norepinephrine and epinephrine bind to the um Alpha and beta receptors we're going to only look at Alpha One but there's beta 1 beta 2 Beta 3 we're going to look at just beta 1 and beta 2. because they do different things in different situations so if we can draw our pathway this first neuron even though it's sympathetic is still going to release acetylcholine and these receptors are still going to be nicotinic excitatory creates excitatory postsynaptic potentials or ligandated but down here this neurotransmitter is norepinephrine and these receptors on let's say the heart or smooth muscles of the bronchioles or blood vessels those are either going to be Alpha One or beta receptors depending on and you may have both as well sometimes you will have both I'll explain that when we get there uh I talked about the neurotransmitters the autonomic nervous system not sure I need to go over this I do want to point out however that in both sympathetic and parasympathetic there are different ganglia and in the sympathetic anybody remember what we call those ganglia and the sympathetic where the two neurons meet or the two neurons synapse nope not the inner neurons so this is peripheral nervous system so if you recall from biology 152 if you were to look at the spinal cord running on the lateral sides of the vertical column we have these little ganglion okay those are the sympathetic chain ganglia that's one of the ganglia we're also called paravertebral and then we have what are called the collateral ganglion and these actually innervate your abdominal uh pelvic viscera uh and then with the uh parasympathetic those ganglia are either really really close to that effector or actually embedded in it and we have what are called terminal ganglia which are really really close or we have the intramural which are actually embedded within the tissue if I ask you anything about that that's from nine two and that would be on the take home part of the exam if I ask you about the gangly it would be on the take home part so section 9-2 is only going to be on the take home yeah you're probably going to have to understand some of the basics to understand 9-3 but now when we look at smooth muscle smooth muscle cells don't necessarily have the axon terminals in um directly on each cell what we actually find is that the motor neuron that would be this the postganglionic cell has these swellings in it called varicosities now smooth muscle comes in sheets essentially and what we have is this neuron as you can see in the picture here kind of goes in between those cells within those smooth muscle sheets and she'll travels down it stimulates the release of neurotransmitters from these varicosities so it does the same thing as far as changing the behavior of the cell it's just that the neurotransmer isn't released at the very end the terminal portion of the Axon it's that these little bulbous parts of the axon contain neurotransmitter vesicles and they actually release their neurotransmitters kind of out to the side of the axon to the tissues that surrounding it that's kind of a key characteristic for smooth muscle all right any questions that's just kind of an intro now we're going to get into looking specifically at the different receptor types associated with the different sympathetic comparisons all right take a minute look that through yeah this is on page 213. so if you can find 213 and have that ready so I'm going to explain this chart and how to read it again I will give you this chart on the test you just need to know how to read it so let's take a if there's no questions let's take a look at this so if you look at the chart it's kind of divided into three areas so right in the middle we have the receptors so we have in green The muscarinic receptors and they're showing us three subtypes there's actually five subtypes we're only going to focus on M2 and M3 and then we have the nicotinic receptors we have the nicotinic receptors associated with those ganglia in the autonomic pathway but we also have the nicotinic receptors associated with skeletal muscles that's something we look at in unit three and over here then these are the receptors the alpha and beta so if I said Alpha and beta receptors what should immediately come to mind sympathetic or parasympathetic sympathetic so if you see a question and I say something about Alpha Beta you immediately need to think okay he's going to ask something most likely about the sympathetic nervous system because Alpha and beta are only associated with effectors connected to the sympathetic nervous system or sympathetic effectors and carrying out those sympathetic responses if I said muscarinic you should automatically think what parasympathetic now if I said nicotinic this is going to refer to obviously what happens at the at the ganglion between the preganglionic and postganglionic cell you're going to need to know what I mean when I say preganglionic and postganglionic two neurons in the pathway an autonomic pathway first one is preganglionic second is postganglionic the ganglion is where neurotransmitter one is released and it's the nn subtype so that's kind of the only thing if I say simple or parasympathetic you can probably probably a good chance that you can ignore this part of that table because we're going to be mainly looking at why does the parasympathetic cause the heart rate to go down when it binds to an M1 receptor or why does the heart rate go up when a certain chemical binds to the M2 receptors and I'll walk you through this okay all right that's one part of these tables now up here we see something that says Agonist and then you have all these names now first off don't memorize the table and you don't need to know what these chemicals do now maybe you already do if you work in healthcare you may already know what some of these chemicals do fine great you don't need to know that because I give you a description typically so an Agonist is a chemical that has the same effect in this case on this table that has the same effect as acetylcholine it's going to bind to the same receptors as acetylcholine and Trigger the same response that acetylcholine would if we look over here on the sympathetic portion a sympathetic Agonist is a chemical that's going to bind to an alpha or beta receptor that's going to have the same response as epinephrine or norepinephrine foreign so what do you think an antagonist is it's opposite it's something that will bind so all these chemicals down here under agonists these are chemicals that will bind to The receptors but they don't actually cause the same effect as the regular chemical would they actually block the receptor sites and prevent in this case here prevent acetylcholine from binding and therefore preventing acetylcholine from changing the cell's Behavior same over here is that these antagonists over here on the sympathetic they will block the alpha or beta receptors and prevent either norepinephrine or epinephrine from binding to those receptors and if epinephrine is supposed to you know uh relax the smooth muscle like in the brachials norepinephrine um or epinephrine I should say well bind to receptors on the smooth muscles then your bronchioles and cause the smooth muscles to relax causing bronchodilation opening up your Airways but if you have a chemical that blocks the beta-2 receptor that's going to keep those Airways constricted and not let epinephrine do its job okay so far so good on how to read this yeah read in my mind I'm sorry go ahead you're gonna get time no go ahead finish so correct so Alpha One so what what this means is that notice that if I were to draw a line like this kind of breaking up all these different receptor types and you can do it on both of them that epinephrine can bind to Alpha and beta norepinephrine can only bind to Alpha One Alpha 2 and beta 1. this chemical here dopamine only binds to Alpha One and beta1 so if I say okay um I can't even read this if I said um whatever that says the only place that that actually binds is to the M1 cells and you're not gonna have to know M1 but uh and it would act as an antagonist so it's going to block the receptor site prevent acetylcholine from binding to it and having the opposite effect that acetylcholine would if it was attached so what I'm going to ask you on the exam is I'm going to say this particular chemical causes this to happen you got to find it and then you have to read the rest of the question then to answer it so for example then norepinephrine binds to Alpha One this is going to cause smooth muscle contraction in the blood vessels if this labetalol attached to the Alpha One receptor that's going to block the effects of norepinephrine which would actually cause that vascular smooth muscle to relax causing the blood vessel to dilate reducing the blood pressure that's the style of question you're going to have what's the difference I'm not sure I found this on the internet probably 15 years ago and I've been using it ever since because it's it's great so I'm not sure why some are bolded and some are not maybe because it binds to more than one yeah that kind of looks like the pattern if it binds to more than one receptor it's bolted I think it combines it just one receptor in that particular class then it's not bolded I guess all right so let's focus then a little more detail on adrenergic simulation so what do I mean by adrenergic what am I talking sympathetic or parasympathetic sympathetic good what's that all right so let's look at I'm missing a page in here somewhere foreign so we know that epinephrine comes from the Adrenal medulla if you look at the table we know that epinephrine is going to bind to Alpha One now you can ignore I will not ask you anything about Alpha 2. or beta 3 receptors and I will not ask you anything about M1 receptors and honestly I probably won't ask you anything on the exam about The nicotinic receptors either so epinephrine as you can tell will bind to The alpha-1 receptors beta 1 and beta 2 receptors you can see that alpha 1 vascular those receptors are only going to be found on the smooth muscle in blood vessels you're going to want to make a note of that smooth muscles associated with arterioles very small blood vessels which tells us that these play a big role in regulating blood pressure vasoconstriction and dilation that the Alpha One vascular what that means is that these are only found on the smooth muscle associated with the arterial blood vessels those are the ones that play the biggest role in regulating your blood pressure they constrict and they dilate beta one those are only associated with the heart so in other words the beta 1 depending on what attaches to it if it's sympathetic what does sympathetic do to the heart sympathetic increases heart rate so when norepinephrine and epinephrine bind to beta 1 receptors they will increase the heart rate but if any of those antagonists bind to The beta-1 receptors they block their beta blockers they block the epinephrine and norepinephrine from The beta-1 receptors which then allow the heart rate to decrease to slow it down so these can be used as blood pressure medications too that's beta blockers um that's how you read this chart now notice that norepinephrine and we can make a note here that norepinephrine this is from the nervous system yes we get a small percentage from the Adrenal medulla as well this will only bind to the Alpha One and the beta one again we're eliminating we're not going to do anything with Alpha 2. so if you find norepinephrine on that chart okay so here's norepinephrine now we're we're skipping this Alpha two stuff so we can see that norepinephrine binds to the Alpha One and we can see that it binds to the beta one it does not bind to Beta 2. which means that any of the smooth muscle associated with the beta 2 receptors can only respond to epinephrine that's what that means now these epinephrine norepinephrine depending on the receptor it can stimulate something or can inhibit something so we can say that they're either going to be an excitatory or an inhibitory receptor or an excitatory or inhibitory response and I already mentioned Alpha and beta receptors many times already foreign and start looking at the specific physiology of these receptors so you should have some large sheets somewhere in your packet it's in the back by the charts someplace what 207 so we're going to look at the alpha ones first and hopefully that'll help us understand why when the alpha ones are stimulated by epinephrine and norepinephrine they will cause um blood vessel dilation or dilate constriction yeah we have a question like my other ones here if you look at uh where those tables go there it is if you look at page 214 you'll see this on the test so I give you the organ and I I put a header on there sympathetic stimulation parasympathetic stimulation and I tell you that uh sympathetic will cause the heart rate to go up it increases the force of contraction and increases the conduction velocity of the blood as it moves through the circulatory system I even give you the receptor types you'll notice that under arteries under constriction we have Alpha One those will cause the blood vessel arteries to get smaller causing an increased blood pressure but also notice that we have beta 2 and dilation now there was a mistake on this chart under parasympathetic stimulation artery dilation cross that off that should not be there I'm not sure how it got there page 214 find the organ artery let's go all the way over to the parasympathetic column cross-off dilation so what this means is that when an alpha one receptor is stimulated it's going to cause the blood vessels to constrict but when the beta 2 receptors on those same cells are stimulated specifically by epinephrine it's going to cause that smooth muscle to relax and I will show you why and we'll compare what the beta-2s do and what the alpha ones do also notice that under the gastrointestinal tract we have certain sphincters with Alpha receptors there's certain Alpha receptors in the liver uh in the smooth muscle of the urinary bladder and so on so pretty much when we have an alpha-1 receptor we're looking at several different places obviously we're looking at vascular smooth muscle that's really how we're going to focus on this but according to our chart there are alpha receptors on other smooth muscles so let's look and you have where those other ones are but let's at least look at and this would be location that's the main thing we're going to focus on so let's look at how it works so Alpha One what neurotransmitter notice I said neurotransmitter what neurotransmitter is going to bind to the Alpha One receptors what's the normal chemical that's going to bind to The alpha-1 receptors well norepinephrine is a neurotransmitter that's what's released from the second neuron but we also notice according to that table on 213 epinephrine which is a hormone because it's released into the blood and travels the body via the blood that will also bind to The alpha-1 receptors and so they have the same response so this is how it works so if this is our chemical so let's say that's epinephrine and norepinephrine notice that there's a g protein here we talked about those before that here's our receptor this is the alpha-1 receptor there's a g protein here well when that epinephrine and orpinephrine binds to the receptor that g protein gets released now this is embedded in that plasma membrane now what's not shown and we're going to add a couple of things is that also embedded in the membrane is an enzyme and this enzyme is called phospholipase C and attached to that phospholipation is kind of a special phospholipid that's that's in one configuration so it ends in ASC phospholipase C it ends in ASE that tells you what about it it's an enzyme so when that g protein is released it activates the enzyme which in turn causes this phospholipid to essentially break in half now in simplifying it and what we end up getting is two additional molecules one is called ip3 inositol triphosphate thank you and the other one is called d a g I glycerol I don't think you need to know the names on the exam but that's what the names mean both of these do different things that are important for changing the behavior of the smooth muscle cells now they're muscle cells we want them to contract they get shorter and when they get shorter they do something in this case we're focusing on the constriction of a blood vessel now inside the cell we have smooth endoplasmic reticulum remember that stuff and inside this is calcium ions well calcium ions are are required for muscle contraction I'm also contraction skeletal cardiac are smooth we want these smooth muscles to contract we have to release that calcium from that smooth endoplasmic reticulum and so what the ip3 does is this ends up opening the channels that allow that calcium to diffuse into the cytoplasm of the smooth muscle cells that then triggers the contraction of the smooth muscles and that's something we address in more detail in chapter 12 of unit 3. so the ip3 is what triggers the release of calcium from the smooth endoplasmic reticulum what haven't we looked at yet the Dag what the dag does it actually opens an ion channel in the membrane and when that ION channel is open it lets calcium into the cell from the extracellular fluid adding additional calcium to allow the smooth muscle cells to get shorter and contract trade with a so when the diacylglycerol is activated it binds to this ION channel which in turn opens the channel and lets calcium move into the smooth muscle cell from the extracellular fluid remember we said way back in chapter six if there's more calcium outside the cell than inside the cell free calcium this calcium that comes in is going to be important for causing those smooth muscle cells the actin and the myosin inside the smooth muscles to actually interact and cause that cell to shorten and because smooth muscles are in sheets typically in tubular organs when they contract that's going to cause the diameter of that organ Hollow tubular organ to get smaller this is why we get vasoconstriction blood vessels getting smaller in diameter I'm debating whether or not to provide a little bit more detail about exactly what calcium does how it does it I'll just say this let's number these so that you can go back and kind of put this in a sequential order now remember on the exam I'm not going to ask you even though we're numbering these I'm not going to ask you what's step two what's step three you can break this down into 100 steps if you want I'm going to break it down probably into six okay so here's step one neurotransmitter binds to the receptor step two that in turn releases the G protein and activates the phospholipase C we have three a so this phospholipid splits into ip3 and 3B splits into ip3 and the Dag diacylglycerol now this isn't a traditional phospholipid that's bane of the membrane this is kind of different it's the same basic structure but it's got more stuff on it no it nope it breaks off and kind of travels through the membrane and attaches to the phospholipation which in turn activates the phospholipase 3. so right now the phospholipase C as an enzyme is inactivated so this G protein is acting as what we would call a coenzyme that without the G protein the phospholipase C won't work it's like a switch yes it would attach to it in a certain spot turning a switch on activates the enzyme which then splits that phospholipid into the ip3 and the DHE so 4A we could say then the dag opens the calcium channel and then 5A calcium Flows In it's all being recorded you can go back and watch it four sorry I guess I should call those B's I don't know whatever so this uh this 4A I guess we should call it 4B because we have 3B here because we have two things happening in the third step that phospholipid splits into ip3 and dag at the same time so really this 4A should be 4B and this 5A should be 5B so the dag then goes and binds to that special Channel which in turn opens the channel and lets calcium move into the cell that's 5B calcium moves into the cell this yeah this would be 4A sorry if I want to keep kind of the processes together so 4A would be then that that ip3 that's formed binds to this smooth endoplasmic reticulum which then opens up calcium channels and lets calcium diffuse out of the smooth ER into the cytoplasm itself six and we're just going to say six because the calcium doesn't matter where it comes from does the same thing so calcium binds to something called calmodulin and you're going to hear that again in in chapter 12. so calmodulin is a protein enzyme that's inactivated and when calcium binds to the calmodulin it now becomes activated calmodulin that then in turn is what triggers the smooth muscle proteins the actin filaments and the myosin filaments inside the smooth muscle cells to interact it pulls on the plasma membrane and causes the cell to get shorter it it triggers the opening of these calcium channels in the smooth endoplastic reticulum to let the calcium out that calcium then binds to the calmodulin which then initiates the smooth muscle contraction process now if we're talking a vascular smooth muscle this is going to cause a constriction of the blood vessel raising the blood pressure so what if somebody was given as a pill an antagonist that attached to the alpha-1 receptor what would it do the smooth muscle contraction it would prevent the epinephrine and norepinephrine from binding and would not allow that calcium to be released or enter the cell calcium is not binding to the calmodulin calmodulin then doesn't initiate smooth muscle contraction remember I mentioned this idea of tone sympathetic tone what we have if we want to maintain a certain diameter of our blood vessel we have to constantly stimulate these alpha-1 receptors and the level of stimulation determines the diameter of the vessel go way back to that first slide so this one right here notice we have more stimulations in a certain unit of time that's going to cause a lot more stimulation of that Alpha One receptor causing more calcium to continue being released because that neurotransmitter does not stay attached to that receptor very long it's going to attach and then an enzyme that Mao monoamine oxidase is going to come in and break it down which means that whatever's happening inside the cell stops and if we want to continue that process we have to continue to stimulate that cell so what an antagonist would do in this situation it would come in it would bind and block that epinephrine and norepinephrine for a short time until that antagonist gets removed from the receptor site so it would reduce the amount of stimulation that that receptor gets limiting the time that those cells stay contracted and in a sense then allowing that dilation to occur and relaxation of those smooth muscles they're not Contracting as much so the diameter isn't as small and when your blood vessel diameter is bigger your blood pressure gets lower something we address more in unit four okay that's how an alpha one receptor works now Alpha One are also associated with the gastrointestinal tract the liver uh the urinary bladder the same thing is going to happen the smooth muscle in those organs when they're stimulated we're going to see the same thing and we're going to then cause like constriction of your uh gastrointestinal sphincters or constriction of the urinary bladder which is going to force urine out of the bladder when that detrudes your muscle and your bladder contracts it's going to push the urine out and you're going to get the urge to go so I just use the example of vascular smooth muscle but there's a lot of places where we do find these Alpha receptors and other smooth muscle cells so this is something you're going to have to spend a little time on I would say write these steps out practice drawing this I believe there's additional diagrams online if there's not I can make just the diagrams available so you can practice on these foreign I don't think you're going to see any pictures of these but if you have a visual embedded and kind of a model in your in your mind then hopefully you can understand this process a little better okay all right let's look at beta one these are much simpler if we look at our table on 213 and we find the beta 1 receptors and look under The Agonist category we're going to see that both norepinephrine as a neurotransmitter an epinephrine is a hormone will bind to these These are associated with the heart so the SA node the AV node and The myocardium the actual muscle of the heart itself so epinephrine and norepinephrine or some type of Agonist binds to the beta-1 receptor step one notice we have a g protein step two is that that g protein is released travels through the plasma membrane and so there's the bottom the inside portion of the membrane binds to an enzyme remember anybody remember the name of that enzyme we kind of looked at this before starts with an A dentalate cyclists again ASE tells you it's an enzyme all right so the G protein then activates is released activates the adenylate cyclase step three is that adenylate cyclase converts ATP into cyclic amp camp this is this everything we've looked at so far involved the second messenger system the ip3 and dags are second messengers cyclic amp is a second messenger this is what actually then triggers the change in the cellular Behavior so what this does this inside the a SA node AV node cells or the myocardial cells there is something called protein kinase another enzyme protein kinase a foreign active but when cyclic A and P is formed it binds to the protein kinase a kind of draw it as a rectangle with a square attached to it now it's active just like we saw that the uh phospholipase C gets activated by the G protein okay well this cyclic amp activates this particular protein so now we have an active protein kinase a so let's see two three four four again and what this does is that in the beta 1 receptors this is going to trigger the opening foreign calcium channels again this is going to let calcium into the cell and we're going to get more into this and specifically what happens in The myocardium and the SA node in unit four or we're going to come back and we're going to look at this again and then this calcium then does different things inside the cell calcium is required for cardiac muscle contraction calcium is required for the SA node to send out and generate the signal which triggers the muscle cells of the heart to actually contract which causes the heartbeat now remember the heartbeat the SA node sends out signals all on its own you can sever all the nervous system connections to a heart the heart's still going to be the nervous system doesn't tell the heart when to be it tells it when to beat faster when to beat slower so there's different G proteins Associated don't worry about that just know it's a g protein it does the same type of thing as G protein we looked at in the alpha once yes so it gets released from the receptor travel through the phospholipid bilayer attaches to the adenylate cyclase activates it which then allows ATP to get converted to cyclic amp cyclic AP binds to the protein kinase a activates it that opens ion channels the other thing that could happen depending on where is that it could trigger the release of calcium from smooth endoplasmic reticulum this would happen actually in The myocardium both of these we'd let calcium in from outside and we'd get calcium released from the smooth ER as well and I come back and talk about this when we look at the physiology of the myocardial action potential okay so would this be considered excitatory or inhibitory receptor it's an excitatory receptor so at alpha one right because we're stimulating something to happen we're not stopping something well guess what beta 2 receptors are inhibitory what oh these are only activated by epinephrine which is not a neurotransmitter it's a hormone thank you now these are found on smooth muscle of involuntary effectors which I guess is kind of a contradiction in terms yeah smooth muscle are involuntary so it's found on smooth muscles so we're talking the um bronchial smooth muscles vascular smooth muscles now this would include the blood vessels in the skeletal muscles the vasculature specifically the coronary arteries and I'll I'll look at those with you specifically in a minute foreign testinal tract the smooth muscle the gastrointestinal tract or no the vascular part of it is so if we look at the blood vessels in the skeletal muscles the supplied blood to the skeletal muscles on those blood vessels we're going to have beta 2 receptors same with the coronary arteries and I'll explain why in a minute and then in the gastrointestinal tract on the smooth muscles that Propel the food forward and mix and churn the food we have these receptors as well let me explain what these do and then I'll come back and I'll talk about what we're seeing here [Music] it acts as the ligand that releases the G protein it just comes from it goes gets to the cells via the blood rather than a neuron so it's gonna it it causes a change in the cellular Behavior even though it doesn't come from a neuron but it binds to the receptor train changes the cellular Behavior and in some instances it acts just like norepinephrine it binds to the Alpha One it binds to the beta beta ones except with beta 2 norepinephrine you might get some but this has a much higher affinity for epinephrine than norepinephrine so in order to activate and stimulate this inhibitory response their Adrenal medulla has to release this epinephrine so step one then epinephrine from the Adrenal medulla binds to the receptor so far this is no different than beta one is it but remember these are found in smooth muscles so even though we're going to see a lot of the same things that we just saw in that beta one these are in smooth muscles beta 1 are associated with the heart so step two then the G protein is released activates at adenylate cyclase and what does that adenylate cyclase do takes ATP converts it to cyclic amp again second messenger foreign here's where it's different than beta 1. remember in the beta 1 it activated protein kinase a now that's in the heart we're looking at smooth muscles now one of the things I didn't mention is that in order to get smooth muscles to contract there is an enzyme called myosin light chain kinase okay it's an enzyme it adds a phosphate to something this is typically going to be active because if we think about and this is associated with smooth muscle this myosin light chain kinase associated with smooth muscle this is going to be active causing the smooth muscle to stay contracted or maintaining some type of smooth muscle tone but if we want that smooth muscle to relax in some way and not contract well we have to inhibit that myosin like myosin-like chain kinase and so the cyclic amp then in step four would bind to that myosin light chain kinase and actually inhibit it and prevent smooth muscle contraction foreign you through a couple more things good question why would we want to inhibit smooth muscle contraction we'll get to that in a second so that's the right question to ask now our beta receptors associated with sympathetic repair sympathetic sympathy do we want our gastrointestinal tract to be pushing food through our digestive tract and mixing lower in a fight-or-flight situation absolutely not do we want our sphincters to be relaxed uh and peeing while we're in a fight or flight no but a lot of times you'll piss your pants if you get really scared okay another and I haven't really spent any time researching why that happens maybe it's a conflict of signals theoretically your sphincter urinary sphincter should tighten up because those Alpha receptors are going to be stimulated in a fight or flight well that could very well be because it could be a very primitive instinct is that you piss yourself as an organism and the Predator runs away because oh I don't want to eat this now you know pelvic muscle and not being strong enough well that's all that's our skeletal muscles though but no but yeah so if you're if your pelvic muscles aren't strong enough you can you know squeeze your pelvic muscles women that have children are encouraged to do those Kegel exercises to strengthen those pelvic floor muscles because remember you have an external sphincter as well which is smooth skeletal muscle if you can you know squeeze those then you can even when that internal sphincter opens automatically you can squeeze that external sphincter a little more with those pelvic floor muscles that keep that from leaking out yeah examples probably because they're using different muscles and can't contract those other ones at the same time right yeah okay interesting okay so let's let's break this apart here so why would we want to inhibit smooth muscle contraction well so here's our let's say here's our blood vessel I'm going to do it this way so here's our blood vessel and let's say that this is in a skeletal muscle blood vessels are everywhere and so here's our Alpha One there's a continuous stimulation of Alpha One maintaining a certain amount of tone and diameter letting a certain volume of blood into the skeletal muscles right with me so far so these are constantly being stimulated by norepinephrine well in a fight or flight situation you're gonna have to use your muscles to get away typically or fight right and so what are you going to need to bring to those skeletal muscles to make sure that they can provide you with the ability to run away or stick around and fight you need oxygen and you need other nutrients all used to make ATP you want to increase the flow of blood to your skeletal muscles so that those cells then have what they need to be able to help you survive so even though and so in fight or flight we know we get increased sympathetic stimulation so that means increased norepinephrine from neurons we know norepinephrine binds to the Alpha One but we also see increased epinephrine from the Adrenal medulla which we know also binds to the alpha one but yet at the same time I'll just draw a little different shape okay this is our beta 2 receptor if this epinephrine are released from the Adrenal medulla in a fight or flight binds to this even though this releases calcium which is important for smooth muscle contraction the cyclic amp released are generated from this beta 2 receptor would actually inhibit that smooth muscle from doing anything even though it's being told to contract over here the activation of that beta 2 is going to stop it and block it and prevent that from happening so if our smooth muscles can't contract what happens to the diameter of the blood vessel in your skeletal muscles it's going to dilate letting more blood flow into that organ delivering more oxygen which your breathing rate is increased the heart rates increase so you're able to deliver a larger volume per unit time but also the volume going into your cells is increased as well this is why you inhibit this is why we can find both Alpha and beta 2 receptors on the same tissue oh this is what happens to cause the dilation of your bronchials you're having an asthma attack and you take your inhaler albuterol that's a beta-2 Agonist it binds to a beta-2 receptor it inhibits inhibits smooth muscle contraction of the bronchial smooth muscles and causes those smooth muscles to relax opening up your Airway um same with the coronary artery blood vessels we want more blood flowing to the heart in a fight or flight because that heart needs more oxygen more nutrients because it's has a higher demand it's going to have to contract more often did that answer your question so that's how the beta 2 works now notice if you compared an alpha one to a beta 2 do alpha ones use cyclic amp no they don't two different mechanisms two different mechanisms meaning you can have two different cellular behaviors when those receptors are stimulated would you find a beta 1 and a beta 2 on the same cell you shouldn't because both release cyclic amp are both activate cyclic amp