Cardiac Action Potential (Cardiomyocyte AP: part 4/6)

[TheTackyGirl]

Awesome!! Thanks so much!

[TheDentAmy]

thank you very much, really good stuff!! but the only thing i would point out is the blurry act of the video :( :(

regardless, AMAZING (Y)

[gigantasaur]

I have also read that beta1 mediated phosphorylation sensitises the cardiac contractile proteins to Ca2+, also increasing force of contraction?

I found this confusing because apparently the opposite effect occurs in smooth muscle, protein phosphorylation reduces the affinity for Ca2+. :/

[sahlinja]

Phospholamban is a protein that normally inhibits SERCA

pumps in the SR. Phosphorylation of phospholamban removes

this inhibition causing increased SERCA activity. SERCA resides in the sarcoplasmic reticulum (SR) within muscle cells. It is a Ca2+ ATPase that transfers Ca2+ from the cytosol of the cell to the lumen of the SR at the expense of ATP hydrolysis during muscle relaxation.

[Guitarristandgoats]

Great explanation, thank you =D

[JumpDeluxe]

To me, as a med-student in The Netherlands, it's quite confusing with the Kalium/Potassium and Natrium/Sodium terminology, but that's just a minor detail. Great videos, very insightful. Keep up the good work!

[moshe7964]

Beyond awesome video.

[rickythegreat462]

Thank you. You should consider being a professor... because I get far more out of these videos than I do from the $40k/year I am paying to go to med school

[villekuj]

Good, except the Ca2+ influx is not all about the ICa,L mediated by the tetrameric CaV1.2 channel protein. Rather, the Ca2+ influx mediated by this voltage-gated channel (CaV1.2) allows the Ca2+ to bind the ryanodine receptor 2 (RyR2) found on the sarcoplasmic reticulum (SR). This causes the RyR2 to open, which in turn causes a much more prominent Ca2+ influx into the cytosol from the SR. This phenomenon is known as calcium-induced calcium release (CICR).

[iceySk8a]

Wait..Where did potassium come from when voltage-gated sodium channels close?

Great Video!!

[uppereast74]

Your videos are exceptional. I'm trying to prepare for a Pharmacology exam

on antidysrythmic drugs and I needed a concise and comprehensive review of the

physiology.

[Alalalalala11]

Can you please tell me what the background music is called? and thank you by the way I passed the physiology course thanks to you.

[okioeni]

THX!!!

[Pharmaman100]

great video

[TheAmyk01]

omg!!! thank u sooo much ure brilliant



[TheAmyk01]

omg!!! thank u sooo much ure brilliant

[Evilbible]

tyvm

[theycallmebruce]

hey this is really good mate, thanks :D

[IamMuhammad]

FOR GOD SAKE

is it the sodium or calcium that triggers the sarcoplazmic reticulam AT CARDIAC MUSCLE CELLS ??

[Lanthanideatoms]

@IamMuhammad

Calcium

[PhilSeitz]

Amazing video, thank-you very much

[JasminUlahannan]

Great video! Thanks. 

[KrakenReturns1978]

@karolin111 Sorryca is right. Myocytes can certainly generate action potentials. In fact several arrhythmias are caused by this mechanism. If you look up delayed-after-depolarizations you will see how this happens. High diastolic calcium leads to acitvation of NCX (Na-Ca Exchanger) which being electrogenic causes a small depolarization of the myocyte, this is then amplified by Na channels leading to full depolarization of the cell. This can then spread through gap junctions to other cells

[KrakenReturns1978]

@KrakenReturns1978 However this is not the normal myocyte function and myocytes would never be described as pacemaker cells so it is a bit of a technicality in an otherwise great video. (assistant prof, physiology)

[sorryca]

@karolin111 All cardiac myocytes have the capability to generate action potentials. People need to do their research prior to posting any more non-sense. I am not mixing up anything.

[jessiandbob]

in the plateux phase calcium influx causes binding of calcium to troponin which causes contraction of cell? then after contraction occurs the calcium leaves the troponin and leaves the cytosol to either the sarcoplasmic reticulum or outside the cell via calcium channels or in exchange for sodium. than sodium is pumped out of the cell via ATPase in exchange for pottasium. Where is this eflux and influx of Na and K represented on the graph?

[tobidre]

this is a cool dude!

[BevyB7]

Thank you sooo much for this video! I was totally confused about all the different channels in the pacemaker cells and cardiac conduction cells and how it all came together but now I understand VERY well! Thhaaannkkss! :)

[spyked1]

perfect video... i'm sharing this with my class. excellent brother.

[eliwoohoo]

Nice video, but I believe that norepinephrine INACTIVATES phospholamban by phosphorylating it, thus preventing it from inhibiting the SR Ca pump, and in this matter increasing the rate of relaxation. The end result is the same, but ACTIVE phospholamban DECREASES muscle relaxation and contractility. Correct me if I'm wrong...

[exracon]

nicely explained

[masqn]

sorry, browser crash

[masqn]

@A01126240 I thought that phase 3 repolarization was due to the slow activation of IKr & IKs. Their repolarizing effect causes inactivation of Ca channels in a voltage sensitive fashion. I didn't think that any of the potassium channels were Ca sensitive. Can you tell me which ones are?

[A01126240]

@masqn I just notice a small mistake in my comment, the platue us due to an increase in K outflux in response to depolarization. This K outflux exactly matches the Ca influx (due to slow Ca dependent channels) and therefore the platue is maintained for a period of time.

[A01126240]

@masqn Potassium channels activated by Ca along with voltage dependent K channels are responsible for repolarization. Right now I dont remember the specific name of the channel but the effect of digitalis can prove my point. (check the next comment, nos enough space)

[A01126240]

@masqn Digitalis have a positive cronotropic effect in heart by inactivating the Na/K pump, therefore increasing intracelular Na concentration. In response to this the Na/Ca cotransporter generates a Ca influx in order to decrease intracelular Na concentrations. The overall effect of this is a higher concentration of Ca that provokes a "shortening" of the plateau (repolarization ocurrs earlier because the Ca dependent Na channels activate earlier) and the positive cronotropic effect

[A01126240]

@masqn I can see you are interested on cardiac physiology, I have many articles related to excitation-contraction coupling, so if yo are interested I can sand you an e mail with some of these. I just read an excelent article about pacemaking and a new theory based on a "calcium clock"

[masqn]

@A01126240 I thought that the delayed potassium channels were activating by the end of phase 2, resulting in an increased conductance to potassium and subsequent repolarisation, closing the calcium channels. They're responsive to the voltage changes in phase 0 rather than to calcium, but their effect is delayed. Is this right?

[adarachara116]

I thought normally Phospholamban inhibits SERCA pumps... And when phosphorylated by PKA through NE, Phospholamban is inhubited... right?

[NourhanKamar]

Thank U very Much for this VEDIO :D

[hasithwicka]

I think you have your potassium channels mixed up; early repolarisation in phase 1 (b in your diagram) is contributed mainly the transient outward current (Ito).

Phase 1 is prominent in Purkinje fibers and in epicardial fibers from the ventricular myocardium; it is much less developed in endocardial cells. The Inwardly rectified K+ channel has conductance that is small for outwardly directed potassium currents but susbstantial for inwardly directed K+ channels;

[hasithwicka]

hence this rectification is important for phase 2 (c phase in your drawing) for preventing excessive loss of K+ during the prolonged plateau where electrostatic and chemical forces both favour efflux of potassium.DELAYED rectifier potassium channels are DELAYED. Activation proceeds very slowly, over several hundreds of milliseconds. Hence does not really contributed to phase 2 (or c in your diagram) but more in repolarisation in phase 3 (or d in your diagram).

[hasithwicka]

Otherwise the inwardly rectified Potassium channel also contributes substatially to the later repolarization phase (related to conductance of this channel strangely outward near the resting membrane potential).This is my understanding from Levy and Pappano, am i mistaken? good luck with your exams

[endtroducing]

very clear explanation, thank you!

[egytta1]

you are a king ,,thanks doctor :)

[sorryca]

you are wrong when you say that the cardiac myocytes can not generate their own potential. The difference between the cells at the SA node are that the SA node have a higher autmaticity, meaning they fire faster than the other cardiac cells making it the pacemaker.

[hyperhighs]

@sorryca

Well yes, obviously if you block the SA node, the heart will continue to beat, albeit at a "slower" frequency because the AV node takes over. But the myocytes themselves are not the pacemakers. They are the contractile entities of the heart. The pacemakers are the SA, AV, and Purkinje cells, listed in order of decreasing automaticity. Please listen next time.

[sorryca]

I did listen you said very clearly 'the myocytes can not generate their own spontaneous potentials' this is wrong. Cardiac myocytes CAN and WILL and sometimes DO generate their own potentials. The myocytes WILL act as their own pacemakers the reason why the SA node is considered the pacemaker is for this simple reason: it has higher automaticity. Why do you think that cardiac myocytes grown from stem cells contract?

[sorryca]

As well everything else was spot on, you just kind of ticked me off by saying 'listen next time' as if I heard you wrong. I wasn't looking for this information for myself, I was actually looking for video of cardiac myocytes and came accross this one and decided to watch it maybe I could use it myself for the tutoring that I do.

[zatchmo1988]

@hyperhighs Actually, any cell in the heart can act as a pacemaker cell. Thats what ectopic pacemakers are. Additionally, when you have (for example) atrial fibrillation, you have multiple ectopic foci other than the SA node firing at the same time which causes the atria to flail around and not contract in a normal manner. This is not as big a problem as if you had ventricular fibrillation since the atrium do very little in filling the ventricles with blood, but the ventricles are the powerhouse

[MrMike00722]

@hyperhighs haha... burn! 

[beti05]

@MrMike00722 idiot

[sorryca]

@hyperhighs Lmao, I remember this video. Weird that you didn't even reply to what I said AND you lied in this comment PLUS you kept the mistake in your video.

[hyperhighs]

@sorryca What's up with your negative attitude? If you find a mistake in any of my videos, just post a correction. I can't reply to everyone, and I certainly can't redo the video. You clearly lack the manners and professionalism of a good-hearted physician, and I would encourage people like you to avoid entering the medical establishment. Thank you.

[tonggiang12]

@hyperhighs I gave a thumb up but I also have to make a comment here that I agree with reply to sorryca.

[tonggiang12]

@hyperhighs I gave a thumb up and also have to say that I agree with your reply @ sorryca. What's up with the negative attitude?

[acetone58]

@hyperhighs he was actually technically correct. All cardiac myocytes are capable of spontaneous action potentials in their own right. This is not limited to SA, AV, and Purkinje pacemaking cells. The reason why the pacemakers are necessary is that very fact actually. The reason is probably more indepth than what would be necessary for your audience but none-the-less it's true. You can easily see this in cultures and there are many diseases which are caused by it as well.

[SunxFlowerxKiss]

@hyperhighs  Could you please post a copy of your notes in pdf form somewhere so we can use it to review later when we don't have the chance to see your video before an exam? PLEASE!

[tarzain]

@sorryca He did answer your question and he wasn't wrong in the first place. Too bad there is no cure for stupid.

[PolishStud101]

@sorryca

He DID reply to what you said. You were just too stupid to understand.

Be gone loser.

[isaiahnbrandon]

@sorryca ... he did reply to your comment. he said SA, AV, and purkinje fibers were the pacemaker. not contractile cells. he is right..

[acetone58]

@isaiahnbrandon I'm not sure what the aggressiveness is. I'd be slightly annoyed if I were in sorryca's shoes as well. He pointed out a valid criticism and instead of being met with a rational explanation was tossed an explanation of something he never brought up.(he was talking about cardiac myocyte automaticity not the various "pacemaker cells) Actually, I would be fascinated to know how you, polishstud, or hyperthighs can explain cultured cells beating WITHOUT generating action potentials

[Obama90]

@sorryca

I agree with what you said. The atria and ventricle fibers do not have pacemaker potentials, but they discharge under abnormal conditions.

Ectopic focus?!

[sorryca]

Thank you an ectopic focus is a good example demonstrating cardiac myocyte atomaticity. They cause a cardiac dysrhythmia.

[spyked1]

@sorryca he's right... but even in the event of a an SA, AV block, the purkinje inherent rate is too bradycardic for survival outside an ICU.

[sorryca]

@spyked1 They do survive outside with no nodes attached. Cardiac myocytes generate their own impulses. I posted this comment a long time ago and I still stand by it. I am in heading to grad school for forensic biology so I'm sure I'm not just takling out of my ass. In this video it is stated that the cells can not generate their own potential, this is FALSE and is DEMONSTRABLY FALSE with a sample. They are not the pacemakers for the simple fact that the nodees have HIGHER AUTOMATICITY

[spyked1]

@sorryca i understand... thanks.

[sorryca]

@spyked1 As has been pointed out by another user awhile back a good example of cardiac myocytes having automaticity is something called an Ectopic Focus. This will cause a cardiac dysrhythmia.

[tamer9891]

he saied that the cardiac myocytes can not generate spontaneous action potential. they can generate action potential but not spontaneous because they do not have the funny Na channels, better for you to hear it againe, thank you

[farric1]

This is very useful for teaching my fellow Biomedical engineers in explaining the ion transfer during the action/potential phase. Thanks for saving me the effort to make a video myself!

[zorasaidzada]

THNX SOOO MUCH u saved me a lot of confused reading! Ypu are a great teacher, excellent video!

[enzofalsone69]

Thank you so much for this!! This is a treat!!!

May i ask, i understand K+ efflux is occuring allowing the membrane potential to go back to -80mV. But i dont understand how the inward rectifyer K+ flow is allowing the cell to become repolarised if its moving inward or am i missing something else?

Also during this amazing explanation of yours could you share please when the Na/K+ exchangers and Na+/Ca++ exchangers are taking effect and what they are achieving?

Thank you for this again!! Enzo

[josiahmoulton]

@enzofalsone69

The inward rectifying current is only inwardly rectifying under experimental conditions (IE in a membrane hyperpolarized beyond -80 mv). Normally it is flowing outward, but it was so named "Inwardly Rectifying K+ Channel" becuase under experimentally induced conditions it will reverse K+ flow into the cell.

[tho99ed]

Thanks, man! You're also helping students from Brazil! =]

[johnwang8]

this is just pro, honestly. bravo.

[mrcalzas]

you REALLY helped me with this one!!!!! i just could not figure out how the fast sodium-channels in the myocytes become activated

thank you SO MUCH!!!!!

[Msmedstudy]

Well done!!! How do you find the time to do all this?!

[virtualetude]

how many times does the action potential happen as it fires from the SA node, just once?

for example when you go through AB and C of the action potential when the gates are opening and closing when exactly is all that happening?

[beachfacey]

aaaaah thank you, you are such a good teacher!! I cant believe Ive been trying to understand this for 2 years and it makes so much sense now!! :)

[medstudentE2008]

Your videos are exceptional! Thank you for providing this resource to all of us.

[BeardmanDeNantes]

Watching this the day before the Great Cardiocirculatory Physiology Exam...

Thanks!

[PacificLight]

Love the videos, they are helping me cram for cadiophys.

[alinafadur]

you say that cardiomyocytes don't have automatism! i've learnt that they have it but is latent ....they manifest it only in some cases...like extrasistole..

[vr00m123]

I was wondering if you could give some examples or some intervals for the X axis (time).

[nurse01241984]

standing ovation!!!!!

[numerid4]

Just to clarify: in the pacemaker cells, sodium rushes in followed by calcium, and then potassium leaves the cell.

In the cardiomyocytes, sodium rushes in, followed by potassium eflux, and then calcium rushes in?

How is this difference in order explained?

Pacemaker: sodium influx, calcium influx, potassium efflux.

Myocyte: sodium inclux, potassium efflux, calcium influx. Right?

[jasona07]

Yep... you definitely just saved my uni career :-)

[harmit1212]

awesome.....u should be a uni lecturer. i am sure you will beat all other lecturers.

[egytta1]

u r ammazing man!!!!

[firefly767]

you are fucking awesome!