 Now welcome back to the bioelectricity lecture series. So, in the last class we talked about the ultra structure of the sculptural muscle and I just introduced the sliding filament theory. So, today what we will do I will introduce first of all I will introduce two terms here the excitation, contraction, coupling apparatus and in that context we will talk about how the excitation reaches and how the contraction in the muscle takes place. So, these are some of the examples just before I go ahead with the details of how the electrical impulses are being transmitted across the muscle and how it leads to the contraction. These are some of the very simple inspiration for developing microelectromechanical system or which is commonly known as MEMS systems where several attempts are being made to develop bio inspired machines which functions by the transformation of electrical to mechanical energy from mechanical to electric energy so on and so forth. So, let us start first of all based on what we have done in our lecture 16. So, we are in the lecture 16. Let us start with the sliding filament theory after sliding filament we will talk about the excitation contraction coupling apparatus and some of the inspiration which could be derived out of it. So, here we are into lecture 17 and these are what we are going to cover going to cover sliding filament theory and then we will be talking about excitation contraction coupling apparatus and how these things inspired bio MEMS is essentially microelectromechanical systems and how such things could be utilized for prosthesis. This is essentially what we are going to cover in this lecture and in this section. So, coming back to the sliding filament theory. So, in the sliding filament theory we have talked about the cross bridges of the actin and myosin filament we have talked about troponin and tropomyosin proteins which are present there. So, we will just a small recap. So, what essentially happens is this when the nerve impulse comes on the muscle surface it leads to the transfer of the impulse and which leads to the contraction of the muscle that is what essentially is happening. So, in other words the excitation. So, when you talk about the excitation contraction coupling excitation. So, if I break down the word excitation is the excitation which is arriving from the electrical impulse electrical excitation and contraction is the movement of the muscle and in this whole process one of the key iron which plays a vital role is calcium. So, if I had to just draw it is something like this here. So, for example, you have the neuronal cell body and which is forming synaptic contact on top of the muscle. So, here you have the electrical impulse coming which is leading to the excitation of the muscle or which is essentially an electrical excitation of the muscle by neuron where this is your motor neuron which is showing by m n and here you have the skeletal muscle S k denoting a skeletal muscle. So, here you are having the electrical excitation reaching and whatsoever sliding movement which is taking place within the muscle sliding motion of skeletal muscle is essentially the contraction of the muscle and this excitation contraction of the skeletal muscle and essentially this electrical excitation and this contraction these two are integrated to form the excitation contraction coupling apparatus. So, this is what we mean by in the first slide when I was telling you excitation contraction coupling apparatus. So, this is what it essentially means as excitation contraction coupling apparatus. So, what we will be talking first is the contraction process the process by which the sliding movement or the sliding motion of the muscle takes place. So, essentially we will be talking about coming back to the slide first of all we will be talking about this part this part of the story we will be talking about and then we will come back to the upper part well the electrical excitation how it reaches. So, in that context we will be talking first about the sliding motion of muscle which is also governed by sliding filament theory now let us move on to the sliding filament theory. So, part of the sliding filament theory we have already discussed we will be discussing the finer details in order to recapitulate back what we have done in our last class I will have to again draw the cross section of the muscle what I have drawn in the previous class remember when I was drawing this cross section. So, this was essentially what I have drawn previous class like this and the lines are slightly off. So, do not worry straight and in between you have like this. So, this was the arrangement what I have already discussed this has been discussed. Now, if you if we kind of looked at it very carefully out here for example, along these along this part pick up another color if you look at it very carefully on this part. So, it looks like something like this should be more or less like and on this you are having the troponin and tropomyosin proteins like this we have already discussed this part is already on this side pick this up this one looks more like you have the myosin heads right. So, the processes what happens is this whenever out here there is a movement of calcium ions say for example, I represent these dots as calcium ions. All of a sudden there is an exposure of calcium ions which are coming here entry of the calcium ions essentially what it does is move on to the next page there are two three things happen. First of all step one of the sliding filament is exposure of the active sites to calcium ions exposure of active sites calcium ions and calcium ions essentially after entering the circle plasma binds to troponin and this calcium ions after entering binds to troponin. Once it binds to troponin after binding to troponin this weakens the bond of between troponin and troponomyosin weakening the bond between troponin and tropomyosin this weakening of the bond between troponin and tropomyosin leads to the troponin molecule then changes position pulling the tropomyosin away from the active site. So, the next step is the troponin molecule changes position and thereby pulling the myosin molecule away from the active site. Thus allowing formation of cross bridges formation of cross bridges. So, this is step one. So, step one let us summarize what is happening the molecules are getting into that whole cross bridges or among those sliding structures and it removes the troponin basically it weakens the bond between troponin and tropomyosin and thereby removing that bond and thereby because the active sites are actually prevented or they are not exposed because on top of the active sites if the troponin and tropomyosin sitting like this as soon as the calcium comes say for example, if this is the calcium as soon as the calcium comes it weakens the bond and it separates out and thereby exposing the active site and then this active site is the binding site which will be our step two. Let us move on to the slides again now we are in step once again yeah now we are in step two. Step two is basically step two is essentially attachment of cross bridges attachment of cross bridges because now the basically the inhibitory or the molecules which are not allowing to exposed is being removed the troponin tropomyosin is gone. So, now the cross bridges can form. So, the active site is all exposed. So, coming back to the slides so attachment of cross bridges basically this step essentially means when the active site are active sites are exposed the myosin cross bridge bind to them binds to them or sorry binds to them. So, this is essentially what is happening is now the myosin cross bridge which is if I represent it like this this is this is in contact with. So, now after this we move on to step three. Step three is essentially something called pivoting pivoting what is pivoting pivoting is essentially in the resting sarcomere each cross bridge points away from the m line if you realize here. So, basically this is the m line. So, they are pointing away from the m lines if you look at these m lines. So, if you look at the structure very essentially very carefully and you will see most of at most of the time they are facing away from the m line. So, this is where you are having the m line fine. So, at the resting they are facing away from the m line. So, coming back resting sarcomere cross bridge points away from m line in this position the myosin head is a term which is used caulked like the spring in a mouse trap and this caulking the caulking the myosin head requires significant amount of energy. So, essentially this is a energy driven process and out here energy is supplied by the ATP molecule. So, they essentially would happen since energy is obtained by at this time energy is obtained by ATP is broken down into ADP plus phosphate and this is the phosphate generation which leads to the energy and this leads to the formation of the. So, after the cross bridge at attachment has occurred the stored energy is released as the myosin head pivots towards the m line. So, this is where basically what happens if I go back this energy what is present there. So, this is what is leading to this motion you see there is a pivoting motion which takes place this is being promoted by. So, essentially the motion is like this whenever it has to you know pull them. So, the motion towards this direction. So, in other word this these two arrow what I am drawing now if you follow this motion is being promoted by the ATP which is releasing ADP and phosphate and this energy which is generated out here this energy actually goes here and leads to that something eventually what is being called is the power stroke. So, this is essentially what is happening here coming back out here. So, coming back from where I was talking about the caulking caulking the myosin heads requires energy and this energy is obtained by as I have already mentioned from the ATP. In caulk position the ADP and the phosphate which is shown here ADP and the phosphate are still bound to the myosin after cross bridge attachment is occurred. So, this is called cross bridge one second has occurred the stirred energy is released as the myosin head pivots towards the M line this action is called the power stroke is called coming back. So, essentially what is happening if you try to look at it it is basically the heads are like that they are unexposed as soon as calcium comes they bind once they bind they make it move like this and this whole motion of the myosin head like this from this to this this to this from both sides if you look back to the picture again coming back. So, there is a conceptual thing you have to understand these head this whole motion out here if you look at it out here this motion this motion what I am showing you in pink color now this motion this motion is critical for the power stroke to take place. So, essentially it is sitting like this and here you have the myosin head which is making it move like this and this whole power stroke is a function of energy there has to be significant amount of energy ATP has to go there bind there and has to release its energy and thereby allowing that this power motion. So, this is what we call as a power stroke and this is what leads to the sliding filament motion sliding filament theory. So, there are few other tail pieces on this before we move on to the excitation part of this. So, coming back so the next step it is out here in is step 4 step 4 is essentially detachment of cross bridge next step because this process is a dynamic process detachment of cross bridge followed by step 6 which is reactivation of myosin. So, this is what is essentially is happening this whole process is being governed by the presence of calcium. So, coming back to the slide where I was showing the excitation contraction. So, electrical impulse reaches transmitted from the neuron to the muscle surface within the muscle surface it has to reach all the way along the three dimensional architecture of the muscle. So, now what will be talking about how that excitation is being transmitted to the muscle and the end goal of that excitation is that there is a contraction which takes place and that contraction is initiated by the release of calcium. So, coming back to the this is a slide. So, this is where we started the electrical excitation reaching and leading to the motion of the muscle. Now, the question is where we started this whole thing is how it reaches all the way down on several occasions we have kind of kind of try to highlight this part how this is happening for that we have to once again let me yeah. So, for that we have to understand the muscle architecture because this is where because of this electrical excitation there is a release of calcium, but how that is actually regulated it is very essential to understand how that calcium release is being regulated at that point of time because that calcium release is the cause of the power stroke what we have just learned. So, now let us see the architecture in another finer details which you let us know exactly what is happening. So, coming back to power stroke reactivation of myosin now we will be talking about. So, the question we are asking now how the electrical impulse from motor neuron M N motor neuron is transmitted to the muscle of course this is happening at the neuromuscular junction and then followed by that how this electrical excitation the muscle leading to contraction and we have seen in that whole process one of the major role is being played by calcium. So, essentially what we have to understand now how this electrical excitation leads to the calcium release how electrical excitation of the muscle leading to release of calcium this is what is essential for us to understand because we have talked already talked about this part the contraction which is governed by sliding filament and the power stroke and everything this part of it. In order to understand this part we have to look at the muscle geometry again we have to revisit the whole muscle geometry. So, muscle structure is that continuous cylinder of all these muscles what you see there are gorge like structure in them there are kind of no we draw the structure they look more like this once again. So, the muscle structure is something like this is only one side I am showing the other side also had and the way the neuromuscular junction is functioning is something like this. So, the motor and plates are sitting like this. So, these are the motor and plates. So, now whenever so let me put it like this. So, this is the motor E p stands for end plate and these are the synaptic terminals out here these dotted structure what I am drawing now synaptic terminals. Now, there these kind of structures what you see this gorge like a structure these are called T T views. So, whenever the electrical excitation is. So, these are when the neurotransmitter are being released. So, the electrical impulse coming from muscle is transmitted to the electrical impulse sorry electrical impulse coming from motor neuron is transmitted to the muscle. So, within the muscle these electrical impulse are now traveling. So, they will travel like this likewise likewise and they will move on like this which way direction they move. So, if you follow my arrow this is how the electrical impulses are moving. So, while the electrical impulses are moving along these T T views within the T T view there are some very specializes structure there are two unique gates which are sitting there and these are voltage gated channels they are sitting out here like this they are sitting out here like this two individual gates one I have shown in violet the other one I am showing as yellow like this both side could be in any side or like it does not matter these small gates which are present there these voltage gated channels what I have shown you now in violet and yellow colors these voltage gated channels sense the electrical impulse within the muscle and what they essentially do is they are attached to another structure here called a part of a structure called SR or SR which is called sarco plasmic reticulum sarcoplasmic reticulum is an interesting structure this is the structure which regulates calcium one has to realize though calcium plays a very vital role but the calcium has to be continuously regulated excess of calcium could become excitotoxic. So, how to regulate the calcium within our individual cells of our body there are certain sponge like organelles called sarcoplasmic reticulum they have a very tightly regulated mechanism by which they release calcium and they pull it back and this sponge action or this releasing and pulling them back as if you are squeezing it the water comes out from a sponge and again you leave it it pulls out pulls the water back. So, as if there is a force which is coming pushing it water comes out and pulls back same way you push it there is some force which comes which throws away the calcium and pulls it back as soon as you really remove the force. So, in this kind of a structures of sarcoplasmic reticulum the way it functions is that it is completely and thoroughly regulated by the voltage gated calcium channels and those two channels what I have drawn are present there these channel essentially regulates calcium. So, these two have very specific names one is called Ryanodyne receptor the other one is called dihydroperidine receptor which is called DHPR and this is also called RYR. So, essentially what happens is that as soon as either one of them it is not really clear which one senses what is still at the molecular details are not clearly do not. So, one of them senses the electrical depolarization and the depolarization is this these are the depolarization waves which are moving within the muscle the as soon as the depolarization waves are sensed by the voltage gated calcium channels one of the voltage gated calcium channel either the Ryanodyne or the dihydroperidine and by the way these names they have got because of the different compounds which are bound to them. So, Ryanodyne bounds to one of the calcium channel. So, it got the name Ryanodyne dihydroperidine binds to another row it got the name dihydroperidine receptor as soon as it binds it as if they are coupled with each other it is something like dihydroperidine Ryanodyne say for example, let us assume Ryanodyne senses it once it senses it tells this one you open up once it opens up the calcium goes out. So, essentially the end result what we see is this calcium from sarcoplasmic reticulum is being flushed into the with inside the cell and is this calcium what you essentially see goes to your that fine structure of which promotes your sliding filament motion ok. So, essentially if I have to kind of you know put them in perspective. So, what is happening is acetylcholine release by motoneuron through neuromuscular junction it leads to electrical excitation of muscle electrical excitation then travels to travels through to t t wheels within the t t wheels they excite or depolarize actually essentially activate Ryanodyne and dihydroperidine receptors or the sarcoplasmic of S R or sarcoplasmic reticulum or sarcoplasmic reticulum this leads to the calcium release by sarcoplasmic reticulum and this leads to the sliding filament motion of the skeletal muscle. So, this part of the story was excitation and this part of the story is contraction and when you add both of them together this becomes excitation contraction coupling apparatus. So, this is essentially is an inspiration to understand how electrical signal leading to a mechanical signal and could we mimic this. So, if you go back to the first slide while I was telling you. So, if you look at it while I was trying to coming back this was trying to tell you sliding filament. So, excitation contraction and could this be used as an inspiration for developing microelectromechanical systems. So, this these are some of the approaches which are currently underway across the world by several people who are working in these kind of areas that could we understand the structure and mimic it and kind of develop biological machines out of it. And one has to realize one of the key component in all these games are the voltage gated channels. If you realize because when the at the neuromuscular junction there is this release of acetylcholine acetylcholine release leads to the acetylcholine well on upon binding on the muscle surface leads to the opening of the cation channels and that leads to the depolarization and the depolarization of the muscle eventually get transmitted leads to the activation of the calcium channel voltage gated calcium channel in the form of an anodine receptor and dihydropyridine receptors leads to the opening of the calcium pores on the sarcoplasmic reticulum. And these pores essentially leads to the release of calcium and this calcium plays a vital role in removing the connectivity between the myosin head and the actin filaments by binding to the troponin and removing or weakening the bond between troponin and tropomyosin. And thereby exposing the active site and on upon binding on the active site it leads to in the presence of of course adenosine triphosphate the energy molecule it leads to a power stroke like this it leads to the sliding. So, it is a very tightly regulated and as soon as that happens the calcium is being pulled back by the sarcoplasmic reticulum it has to be regulated it has to be very time bound very nicely regulated phenomena. So, we look at it very carefully you realize that there is enormous amount of involvement of electrical and mechanical forces inter conversion which leads to such processes. And this is always inspired since the time we have got a fairly good understanding of this whole process in last 20 years there is lot of inspiration could we develop such machines could we integrate machines which could function exactly the way the biological system functions. So, I will close in here for this lecture and we will learn more about in the coming lectures next 2, 3 lectures we will talk more about the retinal prosthesis cochlear prosthesis. So, essentially what we will be doing in the coming lectures we will talk about the structure of the eye and what are the retinal prosthesis cochlear what are the structure of the ear and then we will be talking about the electrophysiology of the cardiac systems. So, I will close in here thank you for your