Cardiac Action Potential - Cellular Basis

Overview

The cardiac action potential describes the molecular basis of electrical activity within the heart's cardiomyocytes. The action potential is a sudden positive shift in the cardiomyocyte's cellular membrane potential, termed depolarization. Depolarization not only initiates contraction within the affected cardiomyocyte (Described in Cardiac Excitation-Contraction Coupling), but also initiates depolarization of adjacent cardiomyocytes. Consequently, depolarization tends to spread in a wave-like fashion throughout the heart as depolarized cardiomyocytes initiate depolarization of adjacent cells.

Shape

The resting membrane potential of cardiomyocytes is roughly -90mV and during full depolarization the membrane potential reaches +20mV. The Cardiac Action Potential can be divided into three basic phases: Rapid Depolarization, Plateau, and Rapid Repolarization. Importantly, the plateau phase is unique to the cardiac action potential and is not found in that of skeletal muscle. This Plateau phase is critical for connecting the cardiomyocyte action potential to cardiomyocyte contraction as described in Cardiac Excitation-Contraction Coupling.

Rapid Depolarization (RD): Characterized by a rapid shift in membrane potential from -90mV to roughly +20mV.
Plateau Phase (PP): Characterized by a sustained membrane potential of roughly +10mV.
Rapid Repolarization (RR): Characterized by a rapid shift in the membrane potential back to -90mV.

Molecular Mechanism

Three basic ion channels are responsible for the cardiac action potential and explain its unique shape. Below we list the ion channels and explain how their coordinated opening and closing results in the cardiac action potential.

Opening of fast Sodium Channels is responsible for the initial, rapid depolarization of the cardiomyocyte. These sodium channels allow for a rapid influx of positive, Na⁺ ions into the cells which depolarize the membrane potential with incredibly quick kinetics. However, these channels also quickly close and thus eliminate the Na⁺ influx soon after maximum depolarization of +20mV is achieved.

Cardiomyocyte potassium channels are induced to open following rapid depolarization and allow egress of positively-charged K⁺ from the cell which is responsible for the cell's eventual repolarization. However, these potassium channels initially display low potassium conductance which increases gradually but slowly. This variable conductance is partially responsible for the unique Plateau Phase of the Cardiomyocyte Action Potential. The initially low potassium conductance only allows for a partial repolarization of the membrane, making possible the Plateau Phase. However, as the potassium conductance builds, it overwhelms all other ion conductances and thus causes the Rapid Repolarization Phase.

Cardiomyocytes uniquely possess a type of Slow Calcium Channel known as the Long, L-type calcium channel. These calcium channels are slow to open following the rapid depolarization phase but remain open for a long time afterwards (i.e. several tenths of a second). Opening of the L-type calcium channel causes an influx of calcium into the cardiomyocyte which initiates Cardiac Excitation-Contraction Coupling. The Slow Calcium Channels are most responsible for the Plateau Phase, because they allow a long time-scale influx of positive ions which exactly balances the initially low efflux of potassium. The balance between calcium influx and low potassium efflux is ultimately the basis of the sustained positive membrane potential observed in the Plateau Phase. Eventually, however, the slow calcium channels close and the potassium channels continue to open, resulting in the Rapid Repolarization Phase.

Initiation and Spread

Although the above description explains how the cardiac action otential progresses following initiation, it does not discuss how the Fast Sodium Channels are first induced to open. Fast sodium channels are themselves "Voltage Gated", meaning that their opening is induced when the membrane potential of a cell reaches a certain, critical threshold voltage. This critical threshold voltage is usually slightly above the cardiomyocyte resting potential, and thus small depolarizations of the cardiomyocyte can induce opening of the voltage-gated fast sodium channels which in turn initiates the full action potential sequence. Consequently, the fast sodium channels in effect enormously amplify low-level depolarizations of the membrane.

The source of these low-level depolarizations is likely sodium ions diffusing from adjacent cardiomyoctyes. Recall from cardiac wall histology that gap junction-rich intercalated discs between cardiomyocytes allow nearly free flow of ions between cells. Consequently, depolarization of one cardiomyocyte will cause spread of influxed positive ions into adjacent cells causing them to reach the critical depolarizing threshold to activate their own voltage-gated sodium channels.

Refractory Period

A key feature of cardiomyocyte electrophysiology is the refractory period of cells to rapid restimulation. Cardiomyocytes enter their refractory period immediately after undergoing an action potential and during this time cannot be induced to undergo another action potential. The phenomenon of the refractory period prevents a cardiomyocyte from being restimulated by action potentials occurring in adjacent cells to which the action potential has just been spread. In the absence of a refractory period, the cardiac action potential could theoretically bounce back and forth between adjacent cardiomyocytes ad infinitum. Such a scenario would clearly prevent coordinated contraction of the heart.

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