so in our previous video we discussed how we can alter the membrane permeability and by altering the membrane permeability we were able to create both an electrical as well as a chemical disequilibrium so the concentration of specific ions like sodium and potassium were different between the cytosol versus the extracellular fluid now in a typical neuron that is at rest that is not sending any kind of signal these neurons have this difference in charge right that electrical disequilibrium so any time there's a difference anytime there is a gradient whether it's an electrical gradient or chemical gradient that represents stored or potential energy so in order for us to establish this there are two main properties that are associated with it number one is the difference in ion concentration specifically of sodium and potassium and of these two potassium is going to be the more important and we'll see why that's the case in addition the second property or second attribute is the relative permeability of the membrane to those specific ions so you are slightly permeable to sodium through leaky channels but you have a lot more potassium leaky channels so you're more permeable to potassium and since potassium is leaving while sodium is coming in there's a net efflux of positive charge leaving behind the negative proteins that are found inside the cell so in order for us to really understand the resting membrane potential we need to recall in module 4 the various factors that influenced rates of diffusion number one size so the ability to fit between the phospholipid heads was important and even if that wasn't the case even if you were too large to fit between the phosphate heads if you're going through a channel or carrier smaller molecules in general diffuse at a much faster rate now keep this keeping this in context when you look at sodium versus potassium sodium is actually a smaller ion compared to potassium number two the composition of the membrane this is very very important not just in terms of what percentage you have of phospholipids and cholesterol we're going to heavily heavily emphasize the amount of protein channels that you have so we're going to talk about leaky channels specifically leaky sodium and leaky potassium channels so those are going to be very important to establish the resting membrane potential and then the gated channels will be important in generating these electrical signals that neurons will use to communicate with neighboring cells the last property that we need to recall that can profoundly impact diffusion is the steepness of the concentration gradient and as we saw in module 4 you have a very steep sodium gradient and you also have a very steep potassium gradient so if i make the membrane permeable to either sodium or potassium there's going to be an influx of sodium or an e-flux of potassium at a fairly rapid rate because of the steepness of that gradient now of course we also have to take into account electrical gradients the fact that if you look at a resting membrane potential the outside has a positive charge and the inside has a negative charge sodium with its positive charge wants to go where there's negative so in addition to a chemical gradient sodium has an electrical gradient it's going down now the reverse is the case with potassium although it's going down a chemical gradient out of the cell potassium is going to an area that there's positive charge so that's sort of a it generates a repulsion as opposed to an attraction so it's not really going down an electrical gradient now another concept that we need to remember is this dynamic steady state how we have to invest energy into the system to maintain both a chemical as well as an electrical disequilibrium and so this is a figure that i took again from module 4 just to again highlight the fact that sodium levels are elevated outside very low levels of sodium inside so there's a very steep sodium gradient as for potassium very low outside very high inside so again there's a very steep gradient well let's just focus on one of these specific ions this also applies to sodium but we're gonna emphasize potassium for the time being so grab a scratch paper and i want you to draw a cell on your scratch paper or on a white board so just draw a very large circle and then start to draw in where sodium ions would be in red and where potassium ions would be in blue so if we follow along let's say we and i'm actually going to draw in one extra sodium here so let's say i have six sodium outside one sodium inside i have six potassium inside one potassium outside now i'm not worried about the fact that there's chloride ions outside and there's proteins on the inside which sort of balance out the charge but if you added up the number of positive charges that you have here so you add up the six sodium with the one potassium i have seven positive charges there now again this is balanced by the negative ions which i'm not showing in the inside i have my six potassium and one sodium so i also have the same number of ions there so overall there is no electrical disequilibrium in this scenario so right now there is a chemical disequilibrium because there is disparate concentration of both sodium and potassium but there is no electrical gradient but what if the membrane was permeable to potassium so what if i have these potassium leaky channels okay and let's just say for argument's sake i have only one channel okay so in which direction would potassium go well clearly potassium is going to go down a chemical gradient and it would leave the interior of the cell to the outside so we would say there's an e-flux of potassium down its chemical gradient now if i did not put any energy into the system that potassium would try to reach a point of equilibrium you tried to get the same amount of potassium inside and the same amount of potassium outside irrespective of how many channels you would have it's just time right it would be much more rapid if i had more potassium channels it takes a little slower amount of time if i only had one potassium channel but eventually you would reach a point of equilibrium so there's an e flux of potassium okay so let's say there's an e flux of potassium and one of these potassiums went out down its chemical gradient okay so what does this do to change the current situation so remember we were at an electrical basically net zero okay but as soon as that first potassium leaves now notice that you have of course you know we can't forget that extra sodium that i drew in here so coincidentally let me just draw it all in here as well so what's going to happen electrically now if another potassium leaves so at this point i still have my six sodium but now i have two potassium outside so there's a net of eight positive charges outside but there's only six positive charges on the inside so i'm starting to make the outside positive and the inside of the membrane negative okay again keeping in mind that the proteins inside the cell are making the inside negative because as more potassium leaves the proteins are too big to leave so they're kind of lingering around on the inside of the cell so at this point because the outside is positive i now have an electrical gradient so we now have an electrical gradient so there's an electrical potential when that potassium from the inside leaves and i have eight positive charges outside and i have six positive charges on the inside so not only do i have a chemical gradient that is driving for the efflux of potassium from this cell i now start to have an electrical gradient and what that electrical gradient does it sort of draws potassium back in so you have a chemical gradient causing potassium to go out but then you have an electrical gradient trying to draw potassium back in so we can no longer just think in terms of chemical gradients because we're dealing with ions and this establishment of an electrical gradient eventually we will reach a point where the chemical gradient will be opposed by the electrical gradient and when that occurs for potassium we're going to call that electro chemical equilibrium so we are not inputting any energy into the system yet this potassium will naturally find a balance between the chemical gradient and the electrical gradient now there is a mathematical relationship for this it's called the nernst equation and don't worry we're not going to do any calculations but it can look at the concentration differences of potassium to dictate what this membrane potential is going to be now keep in mind we're just focusing on potassium we could also add in sodium and sodium itself will also eventually reach a point of electrochemical equilibrium where the chemical gradient and the electrical gradient will counter balance each other now there's a more elaborate equation called the goldman goldman cats equation that takes into account multiple ions but there's one other factor that we need to remember so the one other element that we are then missing then if we have these sodium leaky channels potassium leaky channels is that we do invest a little bit of energy into the system because there's the presence of a third protein the sodium potassium atpase so these three proteins the sodium leaky channel the potassium leaky channel and the sodium potassium pump all of them work together to establish this membrane potential so again if we think about it just in terms of potassium right the point where you have an electrochemical equilibrium the difference in charge across the membrane would be a minus negative millivolt nine sorry minus negative uh 90 millivolts now if we take into account with sodium sodium does make it a little bit more positive so the resting membrane potential although it varies from neuron to neuron we're going to sort of just remember one number it's going to be a minus 70 millivolt so many ions are involved in establishing the resting membrane potential but our primary focus then is going to be on sodium and potassium more over potassium so let's look at this in another way let's say you have a cell membrane and in that cell membrane you have a sodium leaky channel that's sodium because it's elevated outside you would have an influx of sodium down its electrochemical gradient electro because at rest the inside is negative and positive sodium wants to go where there's negative and the outside is positive you also have potassium leaky channels and you have a lot more about 25 times more potassium leaky channels and potassium is elevated inside low levels outside so you would have potassium efflux so there's an e flux of potassium down its chemical gradient so it's not electrical this time because the outside is positive as is potassium now once you have an electrochemical equilibrium where the chemical gradient sort of counteracts the electrical gradient in order to maintain both chemical and electrical disequilibrium you have the sodium potassium pump or sodium potassium atpase and what that does is it uses atp to kick out three sodium and this is why the influx of sodium and the leaky channels of sodium aren't that big of an issue for the resting membrane potential because sodium that comes in gets pumped out and it brings in two potassium ions so notice how three positive charges leave two positive charges come in it reinforces the inside being negative and the outside being positive okay so keep in mind that this is in a neuron that's not sending signal this is a neuron at rest and this difference in electrical potential is called the resting membrane potential or rnp for short in the next few videos we'll talk about how we can further manipulate membrane membrane permeability using chemically gated and voltage-gated channels to alter the membrane potential and that alteration in membrane potential will result in an electrical signal that allows one neuron to communicate with another