If anyone could please clear it up, these drugs effect which phase? Is it Phase 0 (as in the nodal cells)? or is it phase 2 (cardiac myocytes) or does it affect both types of cells?
class 4 antiarrhythmic
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As far as I'm aware, for the cardiomyocyte action potential, they shorten phase 2, thereby prolonging phase 3. For the nodal AP, they lengthen both phase 4 and phase 0, because I'm fairly sure some calcium L-type channels (i.e. those sensitive to lower RMP) open prior to the actual depolarization threshold required for phase 0.
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CCB decrease slope of phase 4, which deceases pacemaker firing rate.
CCB also decrease slope of phase 0 which slows conduction velocity within the av node.
Both these actions are with respect to their pacemaker action potential.
They also increase ERP which will affect phases 0,1,2 and part of 3 in the ventricular action potential because during ERP no new AP can be created.
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CCB also decrease slope of phase 0 which slows conduction velocity within the av node.
Both these actions are with respect to their pacemaker action potential.
They also increase ERP which will affect phases 0,1,2 and part of 3 in the ventricular action potential because during ERP no new AP can be created.
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Can anybody go into more detail about how they lengthen the ERP? Wouldn't shortening the Plateau mean that the Potassium is going to rush in faster and the cell is going to repolarize quicker?
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Yeah I just dont get how that would actually happen. Shouldn't shortening phase 2 consequently shorten phase 3 as well?
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This is a weird concept and does seem counterintuitive. Since Phase 2 of the myocyte AP is balanced by Ca2+ influx and K+ efflux one would think that inhibiting Ca2+ would "unrestrain" K+ efflux.
However, you have to remember that the forces driving K+ out of the cell are both electrical and chemical.
The chemical forces (e.g. concentration gradient) is essentially always in favor of K+ efflux as [K+] is much higher intracellularly than extracellularly. What restrains K+ efflux is the electrical forces inside the cell. That is what causes an RMP.
The idea is basically the same during phase 2 of the myocyte AP. For the discussion below, assume that both K+ and Ca2+ conductance is high (e.g. the channels for the respective ion is open).
I like to think of it this way:
At the plateau(phase 2), RMP is roughly +5-10 mV. At this point, K+ efflux is almost completely determine by the concentration gradient and fairly unrestrained by the positive intracellular potential (in fact, the interior is positive and the electrical forces almost push K+ out of the cell).
As K+ leaves the cell, the membrane potential will rapidly repolarize (become more negative). This will increase the "restraint" on K+ leaving and lower the chemical (concentration) gradient too.
This is where Ca2+ comes into the equation. During the plateau phase, Ca2+ and K+ are basically swapping places. Because calcium is 2+ and potassium is 1+, when the two ions "swap" and "balance" each other, the positive interior charge is maintained at +5-10 mV and it keeps pushing K+ out of the cell. Basically, for every one Ca2+ going in, two K+ have to leave to maintain the plateau.
If you block some of the Ca2+ channels, that "swapping" is slowed down, resulting in an increased Phase 2 and ERP. (I think of it as K+ is leaving more slowly because of the alteration in electrical and chemical forces explained above.)
It is basically the mirror image of what happens when a class Ia or III agent is used that blocks K+ channels. The plateau is maintained because the "swapping" is prolonged. Just because the K+ channel is blocked doesn't mean that Ca2+ rushes in and the RMP jumps to the Ca2+ equilibration potential of +120 mV...
Hope that helps.
However, you have to remember that the forces driving K+ out of the cell are both electrical and chemical.
The chemical forces (e.g. concentration gradient) is essentially always in favor of K+ efflux as [K+] is much higher intracellularly than extracellularly. What restrains K+ efflux is the electrical forces inside the cell. That is what causes an RMP.
The idea is basically the same during phase 2 of the myocyte AP. For the discussion below, assume that both K+ and Ca2+ conductance is high (e.g. the channels for the respective ion is open).
I like to think of it this way:
At the plateau(phase 2), RMP is roughly +5-10 mV. At this point, K+ efflux is almost completely determine by the concentration gradient and fairly unrestrained by the positive intracellular potential (in fact, the interior is positive and the electrical forces almost push K+ out of the cell).
As K+ leaves the cell, the membrane potential will rapidly repolarize (become more negative). This will increase the "restraint" on K+ leaving and lower the chemical (concentration) gradient too.
This is where Ca2+ comes into the equation. During the plateau phase, Ca2+ and K+ are basically swapping places. Because calcium is 2+ and potassium is 1+, when the two ions "swap" and "balance" each other, the positive interior charge is maintained at +5-10 mV and it keeps pushing K+ out of the cell. Basically, for every one Ca2+ going in, two K+ have to leave to maintain the plateau.
If you block some of the Ca2+ channels, that "swapping" is slowed down, resulting in an increased Phase 2 and ERP. (I think of it as K+ is leaving more slowly because of the alteration in electrical and chemical forces explained above.)
It is basically the mirror image of what happens when a class Ia or III agent is used that blocks K+ channels. The plateau is maintained because the "swapping" is prolonged. Just because the K+ channel is blocked doesn't mean that Ca2+ rushes in and the RMP jumps to the Ca2+ equilibration potential of +120 mV...
Hope that helps.
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