Musculoskeletal System | Neuromuscular Junction | Neuromuscular Transmission: Part 1

all right engine 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 and structural 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 neuromuscular Junction and 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 and what is it doing all right so if you look here what I did is I took a crosssection of a spinal cord we're going to take this here let's say midbrain ponds 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 you see here is the cross-section of spinal cord we're not going to go

into Super depth into this because we're just going to f mainly focus on the muscle physiology but just a little bit of anatomy in this back part here the poster part so this is the poster part of the actual spinal cord this side is the anterior side of the spinal cord so posterior side anterior side then if you look here in the anterior side there's a a clump of neurons okay so a clump of these cell bodies specifically that are right here in this horn like structure which is on the 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 and 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 melinated it's wrapped with milin sheaths if it's gray it has no milin so if you look at it 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 are 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 this specific part there is called the anterior but don't be confused if you read in the literature and it says ventril because these are synonyms so they could be either anterior or ventral gray horn okay and so again what is in the anterior or vental grey 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 sematic nervous system so sematic 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 and actually contract this biceps muscle that's voluntary I decided I want to do it that's one thing that the sematic nervous system controls we're consciously aware of it we have voluntary control over our skeleton muscles the other part of the sematic 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 vental gry horn which consists of the cell bodies of the sematic modor neurons what is the sematic nervous system it's where you can it's 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 and 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 it'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 so 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 alpham motor neuron what's actually happening right now well

we're going to talk about the the action potentials in a little bit more detail in the actual neurophysiology 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 stimul ating these actual cell bodies when it stimulates the cell bodies it can generate an action potential so moving down this Aon is going to be having this thing called an action potential and to make it super simple I'm showing it with up arrows to represent that this is an action potential but really

what's happening in just a super simplistic way we're expanding out on in 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 uh 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 threshhold we'll talk about that a little bit here too and once it reaches that threshold these voltage and 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 POS

POS so if you have more cat which just means positively charged ions right if you have cat I 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 so they're moving along this axon it's this and 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 knob like part here so this you know what they call this they can have a couple different terms that you could say this is an axon terminal or they can call this the synaptic bulb right it's 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

it as synaptic bulb 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 what's called an inactivation

gain in 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 ch will open because it's reached a special voltage usually the voltage required to activate these channels is approximately about positive 30 molts okay so once it hits positive 30 molts this channel is then open and look what can flow in calcium calcium can flow in because the activation gate of this channel has been opened because why

because this protein channel is reached its threshold voltage of uh positive 30 molts 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 had 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 this uh depolarizing wave that's a proximately positive 30 molts is moving across this actual cell membrane or we call

it the ax we can call this the actual plasma membrane right this would be called the axolemma 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 Mill volts 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 this synaptic bulb you see we have a lot of these green vesicles they're very special they're actually made now here's here's one thing that 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 are 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 GOI okay and there is specific proteins in there so it actually might have to undergo some type of transcription trans trans ation by the DNA but the PO 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 bulb another thing that's being moved down from this the actual cell body is the mitochondria there's a lot of mitochondria in this area too and we'll talk about why that's important now these black dots are representing a special neurotrans 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 okay I'm going to refer to

it a lot as a now here's the important part acetal choline most people be like oh neurotransmitters they're generally proteins now acetylcholine is not a protein acetylcholine is very very interesting so so it's actually made up of two constituents and now here's the question here's where I actually wanted to get at remember I asked you these synaptic vesicles they're actually made specifically in the cell body but the cocoline is not made in the cell body I can't stress that enough that's said it's extremely important you need to remember acetylcholine is a neurotransmitter but it's not

a protein neurotransmitter 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 aceto COA is the other constituent that we use to combine these

together okay but really we're just going to say acetate Okay so acet acate well we'll see where this acetate actually comes from in a second okay so what are the two components of acetylcholine acetate and choline Co where is 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 through C 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 uh 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 diet okay acetate is coming from where okay remember we have here the mitochondria what's important about these mitochondria what do the mitochondria have in them that's important

with starting the whole kreb cycle activity if you guys remember the mitochondria have a very very very important chemical and that important chemical that they have is called acetal COA but what happens is so let's say I have here my acetal COA here's this acetal COA that we have right we have this acetyl COA coming from the mitochondria because you know that there's a lot of kreb cycle activity occurring with the mitochondria and acetylcoa is the basic starting point for the actual krep cycle to occur now where is this Coline 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 it's coming from the blood and it's actually going to get moved across the actual the actual bloodb brain barrier and then moved into this synaptic Bowl through this special type of choline transporter so this is a Chine transporter Okay now

what's really cool is this acetylcoa and this choline are going to get fused together now what's going to happen is the acetyl COA is gonna it's gonna get it's going to lose the COA 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 acetyl COA what happens is these two molecules react as they react they produce acetal choline but I'm going to write that it's AC because that's what I told you guys I was going to do I was going

to write it as AC okay now but look what happens the COA 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 Bowl through the choline transporter acetyl COA is coming from the mitochondria which are down here in the synaptic bulbs because it's it's an intermediate for the kreb cycle acetylcoa and choline react with one another releasing the COA and synthesizing acetylcholine

but you know this can't happen on its own we need enzymes for this to reoccur so what is this special enzyme this enzyme is cold Co called choline acetal transferase very important enzyme okay so choline acetal transferase is the enzyme responsible for stimulating this step here for converting acetylcholine into acetylcholine all right cool we're good there now we we're coming to the next issue how the heck do I get that acetylcholine into the synaptic vesicle well it has special types of protein Transporters so here's 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 acetylcholine like this right so let's say I just draw a couple acetyl cholin that I transport in now here's the next thing we're trying to bring acetylcholine in but we have to bring it with 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 in 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 this concentration out here of proton 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 a 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 in 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 they'll 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 okay 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 in this process without calcium we would not be able to release this acetool you'll see why so there's

many proteins on this vesicle I just showed some channel proteins but there's a lot of other proteins you know and uh 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 t- 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 or 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 vesicle 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 snapto tagman it's very very important protein okay so synaptotagmin is this Protein that's 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 here very very important protein and this protein is called snapto Brevin okay so that's called synaptobrevin 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 the nice pink they 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 cint taxin so that protein right there is called syn taxin okay so let's just review these proteins again I know there's a lot of proteins and I'm sorry the V snares two V snares what are the two V snares snapto tagman is this purple one snapto Brevin is this blue one okay then we have two t- snares snap 25 in syntaxin here's what's important what do we say calcium came into this actual

synaptic bulb whenever its threshold was reached what calcium does is it acts like a cross link 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 happens here it's a super cool thing snapto brevan and sxin intertwine okay snap 25 also

is involved in that intertwining so look at this all of these proteins start intertwining with one another let's draw it like this draw it like that and then we can say this protein over here the syntaxin is coming over here it's intertwining with this actual synaptobrevin and imagine that these two guys are wrapping around one another and they start pulling this vesicle towards the membrane okay so again what happens here calcium comes in calcium acts as the cross link that stimulates these proteins to link up with one another so originally during 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 bulb okay so now once these proteins intertwine 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 CFT so again once that happens once the snap 25 the syntax

and the synaptobrevin and the 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'll cause the release of this acetylcholine out into the synaptic Clift and then acetylcholine which we're going to represent as this dot here is going to diffuse across this actual synaptic Clift and cause many different types of physiological changes so now to quickly recap and an order a quick recap and Order of everything that's happening here because in the next video

guys we're going to take acetyl coling 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 sematic motor neurons in the anterior ventral grey horn are stimulated we can represent that they're stimulated okay once they're stimulated Action potentials are propagated down the alphao 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 electropositive this wave of positive charges is moving along the cell membrane that is called depolarization so again what is this called here this is called depolarization so this depolarizing current is moving along this actual what is this whole big thing here guys it's called the synaptic bulb once that happens it hits around positive 30 MTS 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 and we talked about acetylcholine where is the acetylcholine coming from okay well the third step was involving specifically the Coline and the actual transport in so this is the third step the third step is bringing the Coline from the diet through this Coline transporter and into the actual synaptic bul the fourth step is taking a acetal COA really in the form of acetate right because you're going to get rid of the COA Infuse the acetate and the choline together in the presence of this choline acetal transferase then the fifth step was trying to

transport this actual acetyl choline into the vesicle but how do we do that the since the acetyl cooline has to move against its 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 past passively which provides this secondary active transport of acetylcholine into the vesicle okay so that was that part 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 which stands for the vesicle snares with the T snares which is the actual proteins on the cell membrane of this whole synaptic bulb what were those V snares the V snares were snapto tagman and snapto brevan if you don't remember these two at least remember this main one snapto brevan he's the really important one clinically and we'll talk about why the other ones are the te- snares and the t- snares were snap 25 in syntaxin 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 synaptobrevin and 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 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 Mill volts up there for the entire time these channels have a special what's called um activation gate their activation gate opens at positive 30 MS also and once this opens a special uh ion starts flowing out this ion is called potassium so again activation gates open at positive 30 mols on this channel and then this potassium starts exiting out of the cell now I want

you guys to think about this for a second if positive ions or cat ions are leaving the cell what is going to happen to the inside of the cell then it's going to become electr negative 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 by the nerst equation it starts moving out and keeps moving and moving and moving out of the cell until the inside of the cell reaches a voltage of approximately -70 molts okay so now again potassium is

going to move out until the inside of the cell has reached a point called re polarization and once it does that it goes into refractory period in other words if this potassium starts leaving out what's it what's the voltage going to reach then the voltage will eventually reach netive 70 molts but not just over here these pottassium channels are all across the synaptic Bol so what happens when they reach 70 molts the inactivation Gates right so the ACT what happens is this this gate will close and calcium can't come in if Cal can't come in

whenever this is happening can the acetylcholine get released no because these synap 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 pottassium 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