CARDIAC ACTION POTENTIAL
Fast -Response Fibers: Cardiac Muscle, His-Purkinje System
Phase 0
Na+ channels open-sodium enters the cell down its concentration gradient (fast INa) causing
membrane depolarization. Rate of depolarization depends on number of Na+ channels open, which in turn depends on resting membrane potential of the cell.
Class I antiarrhythmic drugs can slow or block phase 0 in fast-response fibers.
Phase 1
Na+ channels are inactivated. In some His-Purkinje cells, transient outward K+ currents and
inward C1- currents contribute to the "notch" and overshoot.
Antiarrhythmic drugs have no significant effects on these transient currents.
Phase 2
Plateau phase in which a slow influx of ca2+ (ICa_L) is "balanced" by a late-appearing outward
K+ current (the delayed rectifier current IK).
Antiarrhythmic drugs have no significant effects on these currents during this phase of the
action potential (AP).
Phase 3
Repolarization phase in which the delayed rectifier K+ current rapidly increases as the Ca2+ cur-
rent dies out because of time-dependent channel inactivation.
Class 111 antiarrhythrnic drugs slow this repolarization phase.
Note that during phases 0 through 3 a slow Na' current ("window current") occurs, which can
help prolong the duration of the action potential.
Phase 4
Return of membrane to resting potential-maintained by activity of the Na+/K+-ATPase.
Responsiveness
Capacity of a cell to depolarize, associated with the number of Na' channels in a ready state (see
Na channel below). This in turn depends on resting membrane potential: the more negative the
resting potential (RP), the faster the response.
Conductance
Rate of spread of an impulse, or conduction velocity-three major determinants:
- Rate of phase 0 depolarization-as Vmax decreases, conduction velocity decreases and
vice versa.
- Threshold potential-the less negative, the slower the conduction velocity.
Resting potential-the more negative the RP, the faster the conduction.
Slow-Response Fibers (SA and AV Nodes, Specialized Cells):
Fig: Cardiac Action Potentials in Slow-Response Fibers
Relative Refractory Period (RRP)
A strong stimulus can elicit a response, but the timing will be out of sync with the rest of the
heart, and arrhythmias may occur.
Ratio of ERP to the action potential duration (APD) is a measure of refractoriness, as illustrated
below. Decreases in ERP favor the formation and propagation of premature impulses.
Fig: Relationship of ERP to APD
Fig: Mechanism of Action of Voltage-Gated Na+ Channels
This voltage-gated channel, which is responsible for the fast Na current (INa), exists in three
conformations:
voltage changes. Inactivation of the h gate is slower; therefore, it stays open longer, and the Na
channel is active.
Recovery
Rate of recovery of the Na channel is dependent on resting potential (RP). Fastest rate of recov-
ery occurs at normal RP, and recovery slows as membrane voltage increases. Rate of recovery is
slower in ischemic tissue because cells may be partly depolarized at rest. This reduces the num-
ber of channels able to participate in the next depolarization, which leads to a decrease in con-
duction rate in ischemic tissue. Na channel blockers also slow the rate of recovery in such tissues.
ANS REGULATION OF HEART RATE
Nodal tissue, especially that of the SA node, is heavily innervated by both PANS and SANS
fibers activating M2 and Beta1 receptors, respectively. Phase 4 slope is increased by an increase in CAMP resulting from PI receptor activation and slowed by a decrease in CAMP resulting from
M, receptor activation.
Increase in CAMP will:
- increase upstroke velocity in pacemakers by increase of ICa-=
- shorten AP duration by increase of I,
- increase HR by increase of If, thus increasing slope of phase 4
Decrease in CAMP:
- Does the opposite plus produces a K+ current (IK/ACh), which slows the rate of diastolic
depolarization and thus decreases HR
- Beta blockers prevent CAMP formation, with primary effects on SA and AV nodal tissues.
Fast -Response Fibers: Cardiac Muscle, His-Purkinje System
Phase 0
Na+ channels open-sodium enters the cell down its concentration gradient (fast INa) causing
membrane depolarization. Rate of depolarization depends on number of Na+ channels open, which in turn depends on resting membrane potential of the cell.
Class I antiarrhythmic drugs can slow or block phase 0 in fast-response fibers.
Phase 1
Na+ channels are inactivated. In some His-Purkinje cells, transient outward K+ currents and
inward C1- currents contribute to the "notch" and overshoot.
Antiarrhythmic drugs have no significant effects on these transient currents.
Phase 2
Plateau phase in which a slow influx of ca2+ (ICa_L) is "balanced" by a late-appearing outward
K+ current (the delayed rectifier current IK).
Antiarrhythmic drugs have no significant effects on these currents during this phase of the
action potential (AP).
Phase 3
Repolarization phase in which the delayed rectifier K+ current rapidly increases as the Ca2+ cur-
rent dies out because of time-dependent channel inactivation.
Class 111 antiarrhythrnic drugs slow this repolarization phase.
Note that during phases 0 through 3 a slow Na' current ("window current") occurs, which can
help prolong the duration of the action potential.
Phase 4
Return of membrane to resting potential-maintained by activity of the Na+/K+-ATPase.
Responsiveness
Capacity of a cell to depolarize, associated with the number of Na' channels in a ready state (see
Na channel below). This in turn depends on resting membrane potential: the more negative the
resting potential (RP), the faster the response.
Conductance
Rate of spread of an impulse, or conduction velocity-three major determinants:
- Rate of phase 0 depolarization-as Vmax decreases, conduction velocity decreases and
vice versa.
- Threshold potential-the less negative, the slower the conduction velocity.
Resting potential-the more negative the RP, the faster the conduction.
Slow-Response Fibers (SA and AV Nodes, Specialized Cells):
Fig: Cardiac Action Potentials in Slow-Response Fibers
Relative Refractory Period (RRP)
A strong stimulus can elicit a response, but the timing will be out of sync with the rest of the
heart, and arrhythmias may occur.
Ratio of ERP to the action potential duration (APD) is a measure of refractoriness, as illustrated
below. Decreases in ERP favor the formation and propagation of premature impulses.
Fig: Relationship of ERP to APD
Fig: Mechanism of Action of Voltage-Gated Na+ Channels
This voltage-gated channel, which is responsible for the fast Na current (INa), exists in three
conformations:
- resting or ready state , open or active state
- inactivated or refractory state
voltage changes. Inactivation of the h gate is slower; therefore, it stays open longer, and the Na
channel is active.
Recovery
Rate of recovery of the Na channel is dependent on resting potential (RP). Fastest rate of recov-
ery occurs at normal RP, and recovery slows as membrane voltage increases. Rate of recovery is
slower in ischemic tissue because cells may be partly depolarized at rest. This reduces the num-
ber of channels able to participate in the next depolarization, which leads to a decrease in con-
duction rate in ischemic tissue. Na channel blockers also slow the rate of recovery in such tissues.
ANS REGULATION OF HEART RATE
Nodal tissue, especially that of the SA node, is heavily innervated by both PANS and SANS
fibers activating M2 and Beta1 receptors, respectively. Phase 4 slope is increased by an increase in CAMP resulting from PI receptor activation and slowed by a decrease in CAMP resulting from
M, receptor activation.
Increase in CAMP will:
- increase upstroke velocity in pacemakers by increase of ICa-=
- shorten AP duration by increase of I,
- increase HR by increase of If, thus increasing slope of phase 4
Decrease in CAMP:
- Does the opposite plus produces a K+ current (IK/ACh), which slows the rate of diastolic
depolarization and thus decreases HR
- Beta blockers prevent CAMP formation, with primary effects on SA and AV nodal tissues.
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