Musculoskeletal System | Neuromuscular Junction | Neuromuscular Transmission: Part 1

I ninja nerds in this video we're going to talk about the neuromuscular Junction so if you guys haven't already seen it we made a video previously talking about the skeletal muscle structure then we zoomed in and we took a look specifically at the functional instructional unit of the muscle cell skeletal muscle primarily and that was the sarcomere in this video now we're going to be talking specifically about what's called the neuro muscular Junction in the neuromuscular transmission okay so to start this all off you can kind of see here we have this long motor neuron okay this is a long motor neuron which is basically we have to figure out okay where is this motor neuron coming from what is it doing alright so if you look here what I did is I took a cross-section of a spinal cord we're going to take this here and say midbrain pons medulla here's your spinal cord right there all I'm doing is I'm cutting it like this and we're taking a look at it in this form so what do you see here is the cross section of spinal we're not going to go into super depth in this because we're just going to play mode mainly focus on the muscle physiology but just a little bit of anatomy in this back part here the post here part so this is the posterior part of the actual spinal cord this side is the anterior side of the spinal cord so posterior side anterior sign then if you look here in the anterior side there's a clump of neurons okay so a clump of the cell body specifically that are right here in this horn like structure which is an anterior side and it's gray when you look at it on a microscope right and the reason why is because there's no myelination the myelination is actually what allows for us to be able to see the difference between gray matter and white matter so for example if it's white it means it's myelinated it's wrapped with myelin sheaths if it's gray it has no myelin so if you look at this is the anterior side of the spinal cord posterior side of the spinal cord you're going to have some neurons in here some cell bodies specifically that have no myelination so therefore they're gray and it looks like a horn that is called the anterior gray Horn of the spinal cord so the specific part there is called the interior but don't be confused if you read the literature and it says ventral because these are synonyms so they can either anterior or ventral gray horn okay and so again what is in the anterior or ventral gray horn it is the cell bodies of this somatic motor neurons that is a key word we need to talk about that real quick what is meant by the term somatic so somatic can give you two basic simple definition or two two points one I want you guys to automatically remember that the somatic nervous system so somatic nervous system is voluntary what does that mean to be voluntary so for example if I'm deciding to move my arm right now to be able to flex them and actually contract this biceps muscle that's voluntary I decided I want to do it that's one thing the somatic nervous system controls we're consciously aware of it we have voluntary control of our skeletal muscles the other part of the somatic nervous system is it mainly is supplying the skeletal muscles okay and we're talking about a skeletal muscle right here okay so we're talking about again what is this right here before we get into all of this depth here this right here is the anterior or ventral gray horn which consists of the cell bodies of the somatic motor nodes what is the somatic nervous system it's where you can the nervous system that controls our skeletal muscles and it's under voluntary control okay let's say that this muscle is my biceps muscle and I'm specifically zooming in on one of those muscle fibers or muscle cells what I want to do is I want to contract this muscle cell but in order for me to do that I have to have a stimulus if you guys remember one of the characteristics of muscles is that they're excitable they have to be able to receive stimulus in a form of neural stimulus and then respond to that by having a change in their membrane potential that's what we're going to talk about so let's say that my cerebral cortex sends impulses down right it sends impulses down to my spinal cord and when it goes to the level of the spinal cord which is going to go to my skeletal muscle it's going to send these motor neurons out this motor neuron motor just meaning that's going to the muscle is specifically referred to they specifically refer to this motor neuron as the alpha motor neuron okay that's extremely important I want you guys to remember that the alpha motor neuron is the neuron that is actually going to be going and supplying this skeletal muscles all right so this alpha motor neuron what's actually happening right now well we're going to talk about the action potentials on a little bit more detail in the actual neural physiology but for right now I want you guys to just trust me and understand that from the cerebral cortex impulses are coming down and it's stimulating these actual cell bodies when it stimulates the cell bodies it can generate an action potential so moving down this axon is going to be having this thing called an action potential and to make it super simple I'm showing it with uh pairs to represent that this is an action potential but really what's happening in just a super simplistic way we're expanding out on a end part of that axon so this is still part of the axon what really an action potential is due to is you see these red channels right here these red protein channels are specifically voltage sensitive and they open up at a specific threshold voltage and what happens is sodium is responsible for flowing in to this actual axon through these protein channels now what happens is action potentials are caused by a depolarizing wave and all depolarization is is usually the inside of the cell when it's at rest is generally partially negative so generally the cell is negative I'm going to represent that with just these negative charges what happens is is there's usually some type of stimulus to that neuron that we talked about coming from the cerebral cortex what happens is it brings it to threshold and we'll talk about that a little bit here too and once it reaches that threshold these voltage-gated sodium channels can open sodium rushes in and causes the inside of the cell to become really really positive why does it become positive because sodium is positive so if you have more cations which just means positively charged ions right if you have cations coming into the cell what's that going to do to this negative charge it's going to get rid of that negative charge and now what type of charge are you going to develop inside of this actual axon you're going to develop a lot of positive charges and this positively charged particles are going to move along this axon okay just so they're moving along this axon it's this that's like a depolarizing wave because again depolarization is whenever you're making the cell increasingly more positive okay less negative but again these positive charges are sweeping across and moving across the actual cell membrane now here's what's really cool as the action potential gets down to this big nob like part here so this you know what they call this they have a couple of different terms that you could say this is an axon terminal or they can call this the synaptic bulb right it doesn't matter but really whatever one you prefer I like to say either axon terminal or synaptic bulb I'm probably going to refer to a synaptic Bowl throughout this video so here we have this big synaptic bulb all right as the action potentials are moving down the synaptic bulb it's going to stimulate these black protein channels we're very very special okay so here's the positive charges they're flowing across the actual cell membrane this voltage-gated channel is specific to a special ion and that special ion is called calcium so calcium is usually more concentrated outside of the cell than it is inside of the cell okay but these channels are normally closed because they have is called an inactivation gate an activation gate we'll talk about that more in neuro but what happens is once the voltage moves across this membrane and stimulates a special part of this actual protein what happens is the activation gate will open and this channel will open because it's reached a special voltage usually the voltage required to activate these channels is approximately about positive 30 millivolts okay so once it is positive 30 millivolts this channel is then open and look what can flow in calcium calcium can flow in because the activation gate of this channel is then opened because why because this protein channel is reach its threshold voltage of positive 30 millivolts in order for it to open and allow for the calcium ions to flood in okay so the first thing we said what was the first thing first thing is we have this action potential occurring from sodium ions flowing into the axon and causing a depolarizing wave then what did we say was the second thing the second thing was going to be whenever this is a depolarizing wave that's approximately positive 30 millivolts is moving across this actual cell membrane recall it the axon we can call this the actual plasma membrane right this would be called the axial lemma they call it but this cell membrane here has special proteins these black proteins which are voltage sensitive calcium channels when the threshold of positive 30 millivolts is reached their activation gate opens and calcium floods in and we'll explain why that's important in a second here all right at the synaptic bulb you see we have a lot of these green vesicles they're very special they're actually made now here's that here's one thing and we're not going to talk about super important but these vesicles are generally made where that's that is something we should know where these vesicles actually made are they made here in the synaptic bulb are they made in the axon or are they made here in the cell body that is important because the vesicles are made in the actual cell body specifically by the Golgi okay there is specific proteins in there so it actually might have to undergo some type of transcription translation by the DNA but the port important point is is that these vesicles are actually moved down right so they're moved down by what's called an anterograde transport and an axon transport where you're moving these vesicles down towards the synaptic Bowl another thing that's being moved down from the actual cell body is the mitochondria so a lot of mitochondria in this area - and we'll talk about why that's important now these black dots are representing a special neurotransmitter that neurotransmitter that we're going to talk about is specifically referred to as acetylcholine okay acetyl choline now I'm going to refer to that a lot as a CH okay I'm referred to a lot as a CH now here's the important part acetyl choline most people be like Oh neurotransmitters they're generally proteins now acetylcholine is not a protein acetylcholine is very very interesting so it's actually made up of two constituents and now here's the question here's what I actually wanted to get at mer ask you these synaptic vesicles they're actually made specifically in the cell body but the cecile choline is not made in the cell body I can't stress it enough that it's extremely important you need to remember acetylcholine is a neurotransmitter but it's not a protein or a transmitter so it's not made in the cell body it's made in the synaptic bulb because it's composed of two different constituents that we're going to talk about one part of it is this name choline choline is like a essential like vitamin like nutrient okay so it's kind of like a vitamin like nutrient so one component of acetylcholine is choline and choline is like some type of it's like an essential vitamin like nutrient okay the other component is acetate okay all right our acetyl co a is the other constituent that we use to combine these together okay but really we're just going to say acetate okay so acetate but we'll see where this acetate actually comes from in a second okay so what are the two components of acetyl choline acetate and choline co where's choline coming from do we just have it in our body is it just there no it comes from various different types of nutrient sources we can okay so what happens is you usually get through certain certain types of dietary sources so let's say here's your your gastrointestinal tract oh that's an ugly stomach let me fix that guys let's say here is your actual gastrointestinal tract okay whatever you're eating different many many different types of foods contain the actual choline so whenever you're eating certain types of foods and vegetables and stuff like that it's actually absorbed across the actual GI tract and into the blood okay so choline is kind of an essential vitamin like nutrient and that's coming from the GI tract from the okay acetate is coming from where okay remember we have here the mitochondria what's important about these mitochondria what are the mitochondria have in them that's important with starting the whole Krebs cycle activity if you guys remember the mitochondria have a very very very important chemical and that important chemical that they have is called acetyl co a but what happens is let's say I have here my acetyl co a here's this acetyl co a that we have right we have this acetyl co a coming from the mitochondria because you know that there's a lot of Krebs cycle activity occurring within the mitochondria and acetyl co a is the basic starting point for the actual krebs cycle to occur now where is this choline that we're taking in Co how is it getting in okay so choline is coming and moving you know through the blood and it has special transporters located on the synaptic bulb so here's choline let's say here's our choline there's a special transporter that brings the choline into the synaptic bulb so outside here we're going to have you know maybe the is coming from the blood and it's actually going to moved across the actual the actual blood-brain barrier and then moved into this synaptic Bowl through this special type of choline transporter so this is a choline transporter okay now what's really cool is this acetyl co a and this choline are going to get fused together now what's going to happen is the acetyl co a is going to it's going to get it's going to lose the co a so this reaction is going to happen here so let's take this reaction let's combine these two molecules together so here's our choline and here's our co co a what happens is these two molecules react as they react they produce a CE tool : but I'm going to write that it's a CH because that's what I told you guys I was going to do I'm going to write it as a CH okay now but look what happens the co a should get released out of this reaction okay so that's what happens choline is coming from the diet let's put that right here above it it's coming from the diet certain types of foods are rich in choline then it's brought into the actual synaptic bolt through the choline transporter acetyl co a is coming from the mitochondria which are down here in the synaptic bulbs it's an intermediate for the krebs cycle acetyl co a and choline react with one another releasing the co a and synthesizing acetylcholine but you know this can't happen on its own we need enzymes for this degree occur so what is this special enzyme this enzyme is cold coal called choline acetyl transferase very important enzyme okay so choline acetyl transferase is the enzyme responsible for stimulating this step here for converting acetylcholine choline into acetyl choline alright cool we're good there now we had what we're coming to the next issue how the heck do I get that acetyl choline into the synaptic vesicle well it has special types of protein transporters so here is this pink protein transporter that you see right there right that pink protein transporter is really cool and what it does is we have to concentrate this acetylcholine in so how we do that is we push this acetylcholine in right so I'm going to draw a seed of choline like this right so let's say I just draw a couple of fetal colons that I transport in now here's the next thing we're trying to bring a fetal choline in but we have to bring them something else before I tell you what that is let me actually show you something over here okay so now what we want to do is we want to pump these protons into this area there's a special channel there to get these protons in so what happens is we're going to take these protons and we're going to pump them into this actual synaptic vesicle now generally the proton concentration the synaptic vesicle is higher than the proton concentration out here so if I'm pumping it from an area of what if I'm pumping it this concentration I hear protons is lower and the proton concentration in here is generally higher I'm going against my concentration gradient so that is going to require energy and we utilize that energy in the form of ATP so we're going to break down the ATP into ADP and inorganic phosphate now this proton concentration is being developed in here so now we have a high proton concentration low proton concentration out here that's going to help assist bringing the actual acetylcholine in by like a secondary active transport right because this right here is the direct use of ATP so this is an example of primary active transport and this one over here where what's going to happen to these protons now now the protons have established a concentration gradient right lower out here higher in here so they can move from high concentration to low concentration which doesn't require energy so that'll help to move the acetylcholine into these actual synaptic vesicles or bags of acetylcholine okay so again one more time proton concentration out here is lower than the proton concentration the synaptic vesicle so therefore it's going to require direct use of ATP to pump it against its concentration gradient as the protons are being concentrated in here they establish a gradient difference right more protons out in here than there is out here so the move from areas of high concentration to low concentration through this protein channel but at and when doing that they help bring the acetylcholine into this actual synaptic vesicle ok now we got that part now that we've done that we're going to look at where the heck and how the heck is this calcium going to help us at all in this release of this neurotransmitter because that's what's really cool here and calcium is extremely important processed without calcium we would not be able to release this acetylcholine you'll see why so there's many proteins on this vesicle I'll give sodium channel proteins but there's a lot of other proteins you know and in the beginning of anatomy and physiology usually talk about the cell proteins one of the big ones that I want to just briefly talk about is what's called snare proteins they're called snares and snares there's mainly two types one is called a V snare and that's just proteins that are on the synaptic vesicle okay V for vesicle the other one is T snares and key snares are usually on the actual cell membrane okay there's two main ones there's many many many proteins I'm going to talk about the more common ones are the more significant ones so first one I'm going to talk about is the V snares so there's two main proteins here that we're going to talk about on the synaptic vesical I'm going to draw one here in this this actual purple color this purple protein right here is called synaptotagmin so it's called synaptotagmin it's very very important protein okay so synaptotagmin is this protein is bound to the actual synaptic vesicle now there's another protein bound to the synaptic vesicle let's draw this one in blue so look here there's another protein here's another protein molecule earlier very very important protein and this protein is called synaptic brevin okay so that's called synaptic brevet this protein right here then we have two proteins here on the actual cell membrane of the synaptic bulb okay so now let's draw these proteins so this protein right here is going to be an important protein and let's have one more protein let's do this one in a nice pink they'll have this protein right here okay this red protein is called snap 25 snap 25 all right so we got snap 25 and then over here this pink one is the more important one it's called syntaxin so that protein right there is called sin taxon okay so let's just review these proteins again I know there's a lot of proteins I'm sorry the V stands to be snares what are the two V snares synaptotagmin is this purple one synaptic brevin is this blue one okay then we have two t snare z' snap 25 and syntaxin here's what's important what did we say calcium came into this actual synaptic bulb whenever its threshold is reached what calcium does is it acts like a cross-linked between these two snares okay so between the v snare and the T snares calcium is acting as the link between the two okay so look what happens here calcium comes over here and when calcium comes over into this vicinity he activates through special types of mechanisms he activates these proteins so when he activates these proteins they start wrapping around one another so look what happened here it's a super cool thing synaptic Brabant and syntaxin intertwine okay snap 25 also was involved in that intertwining so look at this all of these proteins start intertwining with one another let's draw like this draw like that and then we can say this protein over here this int axon is coming over here it's intertwining with this actual synaptic brevis and imagine that these two guys are wrapping around one another and they start pulling this vesicle towards the membrane and so again what happens here calcium comes in calcium acts as the cross-linked that stimulates these proteins to link up with one another so originally during a rest they were separated they weren't bound to each other but when calcium comes in these proteins bind onto each other and imagine it clamping and pulling this actual synaptic vesicle down towards this actual cell membrane of the synaptic Bowl okay so now once these proteins intertwining in such a way that it brings the synaptic vesicle enough that it fuses with the cell membrane once this cell membrane fuses with the synaptic vesicle the inside of the synaptic vesicle is exposed to this actual space out here called the synaptic cleft so again once that happens once the snap 25 to syntaxin snap Dobrev inand the Sint synaptotagmin start intertwining with one another and pull the synaptic vesicle towards the actual cell membrane fusing the synaptic vesicle membrane with the actual synaptic bulb membrane due to calcium's presence that will cause the release of this acetylcholine out into the synaptic cleft and then acetylcholine which we're going to represent has this dot here is going to diffuse across this actual synaptic cleft and cause many different types of physiological changes so now to quickly recap in an order a quick recap in order of everything that's happening here because in the next video guys we're going to take a seat of choline and we're going to see how it acts on these receptors how it regulates a membrane potential and all these changes so let's quickly recap everything in an order first thing we said the actual cell bodies of the somatic motor neurons and the anterior or ventral gray horn are stimulated we can represent that they're stimulated okay once they're stimulated action potentials are propagated down the alpha motor neuron what is really happening with this action potential voltage-gated sodium channels are open and sodium is flowing in causing the inside of the actual cell to become more electoral positive this wave of positive charges is moving along a cell membrane that is called depolarization so again what does this call here this is called D polarization so this depolarizing current is moving along this action what does this whole big thing here guys it's called the synaptic bulb once that happens it hits around positive 30 millivolts that's what the depolarizing wave is what happens is that opens up the activation gate on this voltage-gated calcium channel and calcium flows in that was the second step then what else did we say we came over here we talked about acetylcholine where is the acetylcholine coming from okay well the third step was involving specifically the choline and the actual transport and so this is the third step the third step is bringing the choline from the diet through this choline transporter and into the actual synaptic bulb the fourth step is taking acetyl co a really in the form of acetate right because you're going to get rid of the co a and fuse the acetate and the choline together in the presence of this polina CEO transferase then the fifth step was trying to transport this actual acetylcholine into the vesicle but how do we do that the essentia acetylcholine has to move against this concentration gradient we need to take these protons and actively pump them in against their concentration gradient so that whenever they're concentrated they move out of the synaptic vesicle passively which provides this secondary active transport of acetylcholine into the vesicle okay so that was that part and then what else did we say then we said that in order for this acetylcholine to be released we need to have these actual V snares and T snares interacting so that was the sixth step so the sixth step was the interaction of the V snares R stands for the vesicle snares with the T snares which is the actual proteins on the cell membrane of this whole synaptic bulb over those V snares the V snares were synaptotagmin and synaptic brevin if you don't remember these two at least remember this mainland synaptic revving he's do really important one clinically and we'll talk about why the other ones are the T snares and the T snares are snapped 25 and syntax him again if you don't want to remember all of these at least remember syntaxin he's an extremely important protein so the main ones I really want you guys to remember is synaptic revenant syntaxin but here's the thing they're normally not touching one another when calcium is moving in from the synaptic bulb what does he do he stimulates these proteins to cross link with one another and intertwine and pull this actual synaptic vesicle membrane towards the actual cell membrane of this axon bulb or synaptic bulb once they fuse the internal environment of the synaptic vesicle is open to the external environment of the synaptic cleft and acetylcholine moves out by what process we'll say that this is the seventh process and that is the process of EXO cytosis okay one more thing sorry I forgot about the other thing now this this actual axon bulb is depolarizing right well every cell has to rest that's important you see these blue channels right here they're also really special now if you guys remember I briefly talked about it this guy has what's called an activation gate activation gate opens whenever it's at positive 30 all right now what happens is it gets to a certain point right to where these calcium channels they just keep coming in this channel over here is really special because we can't keep this positive 30 millivolts up there for the entire time these channels have a special what's called activation gate their activation gate opens a positive 30 millivolts also and once this opens a special eye on starts flowing out this ion is called potassium so again activation gates open at positive 30 millivolts on this channel and then this potassium starts exiting out of a cell now once you guys to think about this for a second if positive ions are cations are leaving the cell what is going to happen to the inside of the cell then it's going to become electronegative because if you think about it you're losing positive charges so when that happens potassium starts leaving out according to what's called its equilibrium potential that went by the Nernst equation it starts moving out then keeps moving and moving and moving out of this cell until the inside of the cell reaches a voltage of approximately negative 70 millivolts okay so now again potassium is going to move out until the inside of the cell has reached a point called repolarization and once it does that it goes into refractory periods in other words if this potassium starts leaving out let's say what's the voltage going to reach them the voltage will eventually reach negative 70 millivolts but not just over here these potassium channels are all across the synaptic bulb so what happens when they reach negative 70 millivolts the inactivation gates right so the act what happens is this this gate will close and calcium can't come in if calcium can't come in whenever this is happening can the acetylcholine get released no because these synapse no proteins won't be able to link up together that's what happens in the resting period so whenever this actual axon terminal is relaxing or going into a refractory period potassium is moving out to repolarize this whole membrane make it negative which shuts off these calcium channels they can't keep coming in and acetylcholine can't continue to be released okay in the next video guys we're going to talk about exactly how acetylcholine is affecting this actual muscle cell all right at this actual Junction here I'll see you guys soon

Channel: Ninja Nerd

Views: 581,773

Keywords: neuromuscular junction, myology, neuromuscular transmission

Id: OGTMvG7fN-M

Length: 31min 32sec (1892 seconds)

Published: Mon Jun 19 2017