 Welcome back to the lecture series on bioelectricity, so this is the 25th lecture we are starting. So as of now, so we are in the animal electricity module, as of now we have talked about the electrical phenomena in the nervous system, special senses starting from eyes, ears, nose, tongue, touch, stretch reflexes to the spinal cord, up to the brain, memory, sleep, learning, neurological disorders like Alzheimer's, Parkinson's, amyotropic lateral sclerosis, spinal cord injuries, inhibitory excitatory signals, different measurement technique including encephalogram, then patch clamp, microelectrode arrays, field effect transistors and different level of electrical computation what is involved. So now from here we will move on to the next aspect of animal bioelectricity that is in the case of heart which is a completely autonomous system which is functioning in order to you know ensure that we are alive. This is one organ which has a very interesting, I should say very interesting electrical phenomena because it is governed by a set of cells which whose electrical phenomena are entirely different from the another set of cells, they have a totally different kind of ion channels and we will come to that. So before we start this cardiac bioelectricity, let us get some idea about the system itself. So referring to the slides now, so if you look at the cardiac electrophysiology and artificial heart that what we will be discussing, a heart usually beats between 60 to 90 times per minute which is essentially is the pulse rate. So if you back calculate it, so what essentially that means 100,000 times per day heart is beating and it is pumping around 8,000 liters of blood a day. Now you can imagine for a system to function this for the whole life what should be the efficiency of this machine, this is not an easy task, so you are beating like you know 100,000 times. So nature or the way the heart has evolved its electrical processes is different from the nervous system and that you will be evident as you will be seeing the action potential generated by the big chunk of those contractile muscle system which constitute your heart. So this is just to give you a feel that you know your heart is doing some amazing task if your average life span is 70 to 80 years, then this is just a mesmerizing, this is probably one of the most efficient machine you can think of because this machine cannot afford to take rest because if it takes rest then you are in rest forever. So coming to the basic structure of it, if you look at that it is a four chambered structure if you look at it something called a left atrium out here it has a right atrium it is right ventricle it is a left ventricle and essentially what happens is this the right atrium receives if you could see the diagram from superior vena cava the right atrium is receiving the all the impure blood which is coming to the right atrium through the tricaspid valves it moves to the right ventricle the lower chamber from there this is pumped through the pulmonary artery this is the only artery which carries impure blood by the way it goes to the lungs for purification it comes back after getting purified in the lungs through pulmonary vein the only vein which carries oxygen rich blood otherwise and the only artery the pulmonary artery carries oxygen deficient blood so the through the pulmonary vein it comes to the left atrium from the left atrium through the mitral valves you could see the mitral valves here it moves to the left ventricle from the left ventricle through the aortic valve the blood is found through the aorta to rest of the body and this whole process and by the way the right atrium is receiving blood from both inferior vena cava and superior superior is coming from the upper part of the body inferior from the lower part of the body and this whole process has to be synchronized in a very very well regulated fashion if there is any error in this and we are in a big trouble so this whole coordination the way the heart works is coordinated by two interrelated electrical events two interrelated electrical events one is the master other one is the slave and based on them they have the name pacemaker system and contractile system okay so we will be coming to that the contractile system how it is being regulated by the pacemaker system will come in depth but slowly one by one will move on to that so going back slightly the next slide so this is what I was trying to tell you so this is the heart which is receiving sitting in the center out here this is the heart which is receiving from the inferior vena cava you could see the inferior vena cava bringing the blood this is the superior vena cava from upper part of the body bringing the impure blood from the iota it moves to the from the upper chamber it moves to the ventricles from the ventricle it moves although it is lungs to the pulmonary artery and from through the pulmonary vein it is coming back and here this whole circuit is taking place so there are two distinct circuit in the situation one is called the pulmonary circuit the other one is called the systemic circuit pulmonary circuit is the circuit which is exclusively between the heart and the lungs so the pulmonary artery taking the impure blood to the lungs and the pulmonary vein bringing the oxygen rich blood back to the heart that a small circuit so coming back to the slides this part of the circuit this connected circuit between the heart and the lungs is called the pulmonary circuit and then you have the systemic circuit which is the rest of it is a systemic circuit okay so these are the two broad circuit and this much anatomy is essential for you to understand coming to the next slide I will recommend you please go through this link if this link is still functioning you will be able to see the heart contraction and the blood flow there is a nice video out there which I really cannot put it here kindly go through it that I have provided the link for you to go through it it is a really very interesting video okay kindly go through this video so coming back to the next slide this is how the heart architecture is it's kind of a myocardium it's a layer of tissue because this has to be a really a strong organ because this is hundred thousand times per day this is something so this tissue is kind of you know if you see this picture they are kind of you know as if I don't know how many of you've seen this like you know have you seen this you know the ropes the ropes are tied it's almost like if you look at this picture it will look like as if these ropes are tied and these are the valves you see these are the different kind of valves which are like you know kind of you know there's a potion then they close like this and likewise okay so this is to give you a feel about the anatomy of course we are not going to deal with it at this point but just to give you an idea that this is a very very well developed with enormous amount of a strength to ensure that the blood continuously flows and continuously it pumps in this whole process moving on to the next slide now this is what I was trying to tell you there are two circuits which are functioning here one is called conducting system or which is also in other word called the pacemaker system the other one is called contractile system so if you have to give what are the cellular players of the heart so the cellular players of the heart includes the blood vessels which constitute of the endothelial cells what you could see here all the endothelial cells which are making the blood vessels then you have the cardiac muscle cells these muscle cells are the contractile system these muscle cells what you see cardiac muscle cells are the contractile system and then you have the conducting system which constitute your pacemaker cells and in this picture you see this dotted dotted line the yellow line out here this is your conducting system and all these are originated from the cardiac progenitor cell which is mentioned in this picture cardiac progenitor cells are the cells which differentiates into contractile element conductile element of the pacemaker element as well as the endothelial cell and some of these cardiac progenitor cells are present in the adult heart too which could be differentiated into cardiac cells people are attempting the adult cardiac myocytes or adult cardiac progenitor cell to be differentiated into functional cardiac myocytes so this is the overall structure of the heart will be coming in depth but these are the key c the key cell cellular players of the game so if you look at the conducting system conductive system is looks like now if you compare this picture with this picture so this is what I was trying to tell you and the they have different names will be coming to that so the better contrast if you see this picture so this is what you see this from here where you see this star kind of thing from here the electrical impulses originate to give you an idea what this contracting system and conducting system does so before I get in depth we have to realize that heart is continuously beating okay without any electrical signals it does not need it is automatic it is doing so in order to do so there is a circuit with just like a pacemaker just like oscillator it is it is oscillating like this like this this oscillator circuit is absolutely automatic it is this oscillator circuit exists because it has a very unique combination of iron channels which are totally different from nine channels we have dealt with okay these oscillatory circuits which are present there this oscillatory circuit ensures and this what you see out here what I am outlining out here this is this oscillatory circuit which ensures rest of the heart functions so this oscillatory circuit number in terms of the number of cells is very very few with respect to the rest you can see I mean how much area the rest of the heart is how much those cells are constituting this oscillatory circuit constitute the conducting system or the pacemaker system and whenever whenever you hear that somebody is having have a implanted pacemaker that essentially means that this person's conducting system is in trouble it means within this circuit there are certain errors the signal the oscillatory circuit is unable to send this oscillatory message all across that circuit always remember this this will help you to realize and when I was telling you in the beginning of the lecture the master and the slave so this conducting system is the master system which regulates the slave system which is the contracting system so let's move on to the next slide so this is how this whole circuit works so this is where if you go back to the previous picture this is what is called Sino arterial node this is star sign Sino sinus this is Sino arterial node and from here the electrical impulse is spread Sino arterial node to atrial synchium so this is the atrial synchium where it is a spreading okay and there is a rate so electrical impulse is spreads from the sinus node throughout the left and the right atria so those blue lines what do you see out here spreading so the electrical signal is spreading like this automatically the right atrium it will spread faster as compared to the left atrium because it will take some time to reach to the left atrium because of the sheer distance now this node this is the if you again you have to refer to this so this is called AV node if this is called SA node SA node is this one where my cursor is now once again yeah so this is where you see this this is SA node Sino arterial node and this is AV node connected by three connect three connections okay coming back in the Sino arterial node through the atrial synchium through the junctional fibers so these junctional fibers are these ones okay through the junctional fibers it reads to atrio ventricular node which is this AV node atrio ventricular node from the and the electrical impulse spreads from sinus node throughout the left and the right atria now next what happens from the atrio ventrary node which is also called AV node the signal gets split up into two you could see that the signal is kind of you know signal is like this when there is a circuit is moving like this there is a splitting of the circuit you could see in the picture that the circuit is a splitting and part of the impulse is reaching the left ventricle and part of it is reaching the right ventricle and this further split up so to the left bundle bundle branch which is called bundle of he's he's bundles these are called HIS you could see the arrow showing the he's bundle from the he's bundle to the left bundle branch and the light brand bundle branch from the AV bundle to the bundle branches to the parking G fiber to the ventricular synchium so this is how the spread of electrical impulse happens in the conducting system this is how it is being coordinated and this happens at a specific frequency continuously this oscillator functions at a specific frequency of course there is a upper and a lower limit of it but this is how the oscillatory circuit functions and there are sympathetic and parasympathetic control which regulates some of these oscillatory frequencies but when in this circuit when does the circuit what I showed you out here whenever there is an error or there is a blockage in any of this part so what happens is that signal is not transmitted and that's where you need the intervention intervention of prosthesis that's where pacemaker circuits are to be introduced pacemaker is nothing on the surface of the heart or on the body you basically put another oscillatory circuit of electronic oscillatory circuit we generate signals to ensure to compensate for the drawbacks of that existing conducting system so from here let's go on to the next slide which is slightly more complex slide which will give you an idea about the time window so at the 0 0 time point it is starting 0.03 and if you if you read through the sinus node sometimes called the sinus arterial node serves as the heart pacemaker emitting an impulse that result in an action potential okay the cells in the node have almost no contractile element but are connected directly to the atrial fiber so that the action potential spreads immediately into the atrial cardiomyocytes and is transmitted to the entire atrial muscle mass okay so if you look at this propagation time from 0 0 0 0 3 2.0 0.16 0.17 0.17 0.18 likewise if you if you look at it so here it reaches at 0.21 where is it 0.22 just because it has to travel slightly bore on that side okay so this is how the signal is moving through and based on those time number points you could see how the signal is moving so again from sinus node to the AV node from the AV node to the bundle of ease to the left bundle of ease to the right bundle of ease once again another video if you will get see whether this video is functional please go through this one okay now coming to how these are linked with each other so when this conductile system is conducting this thing the electrical impulses moves from so you have to realize one thing if I go back to some of the very early slides let me go back okay here so there is a sequence of event which is taking place here from the right atrium the blood is reaching both the right right and the left atrium from it is pumped here from here it is pumped to the you know the pulmonary artery likewise so this fashion has to be synchronized blood reaching right atrium moving to the right ventricle from the right ventricle it is moving to the pulmonary artery similarly the blood coming from the left atrium coming to the left way atrium to from the pulmonary veins moving to the left ventricle and being pumped to the rest of the body. This whole process has to be coordinated in a very systematic fashion, there has to be a system by which you can coordinate that. So, what essentially the conducting system does is the conducting system the electrical impulses which are generated by the conducting system here are transmitted to the contractile system. These are the contractile system or the cardiac myocytes what you see here. So, these are the membrane potential of the or the action potentials of the SA nodes or the conductile system and they spread to the heart muscles which are the these are the heart muscles. So, these are the action potentials of the pacemaker and these are the action potentials of the cardiac myocytes AP stands for the action potential. Now, what is ECG and EKG how it is linked to the conductile and contractile system to the heart. This is one of the fundamental question which you know. So, coming back to the action potential of pacemaker. So, first of all what we will be doing we will be talking about the action potential of the pacemaker cells because there are two kinds of action potential you could see here. This is one set of action potentials which are generated by the conducting system and there is another set of action potential generated by the contractile system. So, first of all we will talk about the membrane potential of the conducting system and then we will be talking about the action potential of the contractile system. So, coming back to the action potential of the pacemaker cells or the conducting system action potentials it is very interesting. So, here it will realize that these pacemaker cells do not have sodium channels. So, as of now in the nervous system whenever we have talked about action potentials. So, what essentially we have talked about is the action potential is started a cell sets at minus 70 or minus 60 or minus 70 or minus 80 millivolt from there some impulse comes some ligand comes and binds or some light falls on it and the membrane potential shifts to say minus 40 minus 50 from there it is all an action potential is generated. But then in the case of cardiac pacemaker cells the story is totally different these cells do not mark my word very carefully do not set at minus 80 they set somewhere around minus you know minus between minus 40 between minus 40 and minus 50 they are spontaneously active they do not need any electrical impulse they do not need any kind of you know something to pull them. So, if you see the graph now you will see they are sitting at around minus 40 around minus 40 and minus 50 they are spontaneous this activity is spontaneous. So, essentially they do not have they have they because they have slow inward current unlike unlike their counterpart in the neurons where there is a fast activating sodium current they have slow sodium current and they have a voltage gated calcium conductances these are mostly regulated by the calcium conductances and they set out here and from here they can over shoot a over shoot 0 you see the action potentials. So, these are the 0 is the depolarization phase as opposed to the ventricle the muscle action you will see the difference between it and the phase 3 is the repolarization phase. So, if you look at the monophysic action potential of the cardiac myocyte. So, this is what is happening they are sitting at around minus 50 or minus 40 between minus 40 and minus 50 out here in the phase 4 slow sodium influx very slow sodium influx followed by a calcium influx followed by a potassium influx and they come back and again they goes back because of the so sodium influx. If you look at it as opposed to if you look at it because of the slow inward current of sodium and a voltage gated increase in calcium conductance via T channels there is a spontaneous depolarization which is taking place and if we in this picture. So, if they if this is the whole thing then the green green line is showing the complete process. So, this these are the individual ionic conductance you see calcium and there is a slow inward sodium. So, it is the calcium which is the game changer. So, these cells do not set at. So, one of the take home message from this is these cells do not set at minus 80 millivolt. They are sitting at minus between minus 40 and minus 50 millivolt and they are spontaneously active because of the slow activating because of the slow moving sodium channels and coupled with a high percentage of calcium channels. So, they are spontaneously active throughout their life. So, this is how the conducting system is automatically spontaneously function like an oscillatory circuit. They oscillate like this. So, this is the monophasic action potential of cardiac fire pacemaker cell. Now, moving on to the action potential velocities if you if you look at it these are the different conduction rates. So, these cells now in order to understand this what you have to go back to this picture out here. So, at the different part of this circuit there are different kind of pacemaker cells and they have different properties depending on because since I have covered the anatomy. Now, if you see this table that will give you an idea that at the S N O their conduction velocity is 0.05 into per second then at arterial pathway it is 1 this is far more higher and with the per king cells it is even much more higher. So, these different velocities in actually ensures that they have different concentration and different kind of ion channels, but they all sit at between minus 40 and minus 50 millivolt action memory potential. So, that they are spontaneously active. Now, talking about the action potential of the cardiac myosites we have talked about the conduction system we have not talked about the contractile system. Let us look at the contractile system now now we are moving on to the contractile system and I have already shown the connection between the contractile and the conduction system out here. So, these on the right hand side these violet color are the conduction system and this whole process is the conduction system. Now, coming back to the contractile system cardiac myosites can be divided into work cells and pacemaker cells. The work cells have a large stable resting membrane potential just like the neuronal counterpart the contractile system sits at minus 70 minus 80 millivolt and displays a prolonged action potential with there is a difference of course, which you will come across. And whereas, if you compare in the red the pacemaker cells have a smaller unstable resting potential and spontaneously depolarized generating intrinsic this is very important to note intrinsic electrical activity of the heart pacemaker cells are found in the sino arterial node and the and the atrio ventricular AV nodes cells of the bundle of he's and some park engine cell are also capable of spontaneous firing be very careful reading through these lines because this is the most characteristic feature your contractile system follows the membrane potential of the neurons minus 70 minus 80. Whereas, your pacemaker system do not sit there they are spontaneously intrinsically active coming moving on to the next slide how the cardiac myosites looks like. These are the contractile element this is how they look like if you take the cross section this is derived from several people who are patterned them and you know they have grown them in a specific pattern that is how they look like. And they are all you see these lines they are all connected with each other using gap junctions gap junctions are kind of you know between two cells there are connectivity. So, automatically this whole structure does not need to have the synaptic connection between individual cells they are all connected with each other using pipe like structures and those pipes are called gap junction gap junctions. So, between two cells there is a physical pipe which is connecting one cell to another cell likewise. So, these cardiac myosites or the work cell or the contractile cell which over we want to express it as long as you understand the whole concept they their morphology is something like this what you see now from here. Now, let us see the monophysic action potential of the cardiac myosite. So, again see it is sitting at minus 90 millivolt there is fast activating sodium current which essentially overshoot 0 at plus 10 millivolt plus 10 millivolt this is the difference between cardiac myosite and other neuronal third types. This is where you see there is a lot of calcium ions which in flux taking place out here this is very interesting lot of calcium getting in and it holds the cell at the positive potential for a prolonged period of time. Why is it so possibly because these cells have to do their activity for all your life all your life. So, this is the zone where they are in a kind of you know they are not physically you know contracting they are just kind of you know slows down there is a you know this is kind of you know they need some time to recover all the channels and everything. This is this phase this Plato phase what you see lot of calcium and potassium moving in along with potassium because this is the this is the zone where there is in the neuronal cell we observe that there is an entry of only potassium, but here you see there is a huge entry of calcium along with it this is the zone which ensures the cell come remains in a slightly rest situation and then it shoots the next action potential because it has to continuously shoot action potential. So, moving on to the next slide. So, this is what is happening entry of sodium entry of sodium entry of calcium then potassium is going out and this is further bringing it back and this whole process is taking 300 milliseconds. Now, if you compare this 300 millisecond with other neuronal types in realize that this is far bigger as compared to other neuronal cell types. Now, moving on to the next. So, membrane current that generates a normal action potential. So, these are the different component. So, if you go through it this is this has been taken from American Heart Association as a it has been acknowledged. So, you will see from the resting potential which is at minus 80 these are the different components potassium component sodium component in a calcium component several other and the different pacemaker how they are regulating this whole process the membrane current that generate a normal action potential. So, that general normal. So, there is a resting there is an up stroke there is an early depolarization there is a plateau phase there is a final depolarization phase kindly go through this very carefully because I mean this is going to you know enrich your understanding about how the heart is functioning from here back to if you remember while I was talking I talked to you about the rhinodyne receptor and dihydropyridine receptor. So, action potential leads to the motion or movement of the sliding sliding motion which is regulated by the sarcomere. So, this is what you see the electrical impulses leading to the movement of the muscle through the excitation contraction coupling apparatus in which mostly involve the rhinodyne receptors and this has a lot of this is of immense importance in the pharmacology there are a lot of disorders which are observed in that rhinodyne receptors this is what you see this is where it is happening this is where the action potential travel and this is the zone where the rhinodyne dihydropyridine. So, electrical impulses coming and electrical impulses leading to the excitation of these muscle cells and this is where dihydropyridine and rhinodyne receptors are present and they lead to the efflux of the calcium in this these are both are calcium channels of course, this calcium leads to the contraction of the muscle in the sarcomere. So, this is this is a site of hot site of pharmacological interest. So, coming back again we are superimposing some of the tracings of the calcium transient calcium and these are the traces of the calcium recording. So, if you remember while I was covering the last lecture of the nervous bioelectricity I talked to about imaging calcium the ways of calcium which are moving through and heart is a very prominent organ there where this kind of waves of calcium waves are being studied in greater in greater details. So, this is one such example where it has been shown I have given you the reference also you can go through the reference that will help you and this is exactly the reason why I introduce this is what you see are the calcium influxes which are moving through your imaging calcium. So, if you see so what you see that the yellow thing this is the wave which is moving through a cardiac myocyte this was was a trying to highlight in the nervous bioelectricity that there are calcium imaging techniques which are being used. So, near you can see how the calcium imaging is being done. So, you have dyes which changes their color with the influx of calcium and you what you are measuring is that change in color in the form of a wave you see there is a and this is time 0 8 66 133 267 these are the seconds at different seconds how the calcium wave is generating. So, from here change see the changes here which become more intense more intense and it becomes really intense as it moves through and it is now dying out. So, this is moving through moving through the cell a wave moves through like this. So, this wave emotion is the calcium wave what I was trying to highlight. So, if you do a comparison now of the action potential this is what I have giving you an action potential comparison I told you this is almost 300 milliseconds. Now look at the contraction of a skeletal muscle which is far less it is nothing for a skeletal muscle contraction. So, there are two muscle type with a totally totally different action potential and as a matter of fact a smooth muscle if I could have added here you please go through all the reference text book you will see the smooth muscle also have a different kind of action potential pattern. So, it is the time. So, if you compare it cause the sodium entry duration 3 to 5 second ends with the closure of voltage regulated fast sodium channels then comes the plateau where the causes calcium entry duration almost of 175 milliseconds ends with the closure of the calcium channels repolarization where potassium loss starts and then of course followed by that you have this the sodium potassium ATP is pump calcium pumps and everything comes into play which ensures to pull back the calcium and getting the getting the sodium out and getting the potassium in. So, this is a comparative picture which I wish you people really go through very very carefully because this is going to help you to realize how the heart functions for all your life because the act all your this skeletal muscle does not have to function all the time when there is a impulse it function that is it it has a lot of time to take rest, but your heart does not have any time to take rest it has to continuously function kindly go through this very very carefully. Now, a comparison of the action potential generated by the pacemaker and the ventricular cardiomyocytes it could be this is it is written ventricular cardiomyocytes it could be the upper chamber cardiomyocytes also. So, if you compare it the work cells or the cardiac or the cardiac myocytes they have a larger stable resting membrane potential mp stands for membrane potential whereas pacemaker cells have a smaller unstable membrane potential action potential in terms of action potential they have prolonged ap stands for action potential with a plateau whereas pacemaker cells are spontaneously depolarized generate intrinsic electrical activity of the heart. Location right and left atrium and the ventricles whereas pacemaker cells are found in the SA node AB node bundle of he's and parking g fibers iron movement sodium calcium and potassium movement in contrast of the cardiac myocyte action potential there is no fast inward movement of sodium ions during you could you should add this word fast movement of sodium ions during depolarization this is the overall comparison between the two and in terms of the diagram if you look at it look at where they are resting this is resting at minus 80 this one is resting at between minus somewhere between minus 40 and minus 50 and these are the different phases what I have already highlighted if you go through those phases it is it is very fairly clear and the impulses which are generated from this oscillator circuit is being used by used to activate the cardiac myocytes which are present there. So, this comparative picture is very very essential for you people to you know kind of you know take in mind that you know how beautifully this whole system is synchronized because as of now we are talking to the level and afterward we will talk about the EKG is where this is the overall electrical activity because of these two processes which are working hand in hand. So, now comes the question what is ECG or EKG and how it is linked with conducting contractile system of the heart. So, I will close in here with this lecture in the next lecture we will start from here. So, to summarize what we have learned as of now. So, we have dealt with the anatomy of the heart we have talked about the different cell types of the heart we have talked about two different contract conduct the two different electrically electrical elements the contractile system and the conductive system where conducting system is acting as the master and contractile system is acting as the slave. And the impulse generated by the oscillator of the contractile conducting system is transmitted to the conducting contracting system and we have made a comparison between the electrical properties of both of them. So, I will close in here in the next class we will talk about the ECG and the EKG. Thank you.