Excitation-contraction coupling in myocardium

INTRODUCTION

Excitation-contraction (E-C) coupling refers to the series of events that links the action potential (excitation) of the muscle cell membrane (the sarcolemma) to muscular contraction. Although E-C coupling in myocardium is similar in many ways to skeletal muscle and smooth muscle, there are also critical differences. The cyclical nature of cardiac contraction and the importance of myocardial relaxation to cardiac pump function requires that any discussion of E-C coupling also consider the events terminating the muscle twitch as an integral part of the subject. Modulation of muscular function is said to affect inotropy (the speed and strength of muscular contraction) or lusitropy (the ability of the muscle to relax). Increased knowledge about E-C coupling has been a key to understanding both the inotropic and lusitropic states, and it continues to be useful in developing improved therapy for congestive heart failure and cardiogenic shock.

This is a brief review of cardiac excitation (the myocardial action potential) followed by a description of muscular contraction. E-C coupling is then presented as the transduction of a membrane signal (the action potential) to an intracellular effector (the contractile apparatus) by way of a second messenger (intracellular free calcium [Ca2+]).

MYOCARDIAL ACTION POTENTIAL

The resting membrane potential of the myocardial cell is cell interior negative (-90 mV), and is primarily determined by the ratio of intracellular-to-extracellular potassium as predicted by the Nernst equation. The action potential is a temporary depolarization of the membrane. It is caused by transient changes in membrane conductance of several charged ions, especially sodium, due to the opening and closing of ion-specific channels in the membrane. This process can be summarized as follows (graph 1 and movie 1) [1]. (See "Myocardial action potential and action of antiarrhythmic drugs".)

• Rapid depolarization (phase 0) occurs when the resting cell is brought to threshold, leading sequentially to activation or opening of voltage-dependent sodium channels, rapid sodium entry into the cells down a favorable concentration gradient, and a cell interior positive potential that can approach +45 mV. The marked depolarization results in voltage-dependent inactivation of the sodium channels and cessation of the inward sodium flux. Calcium channels also open during depolarization but the onset of the inward calcium flux is much slower.
• Phase 1 repolarization is primarily due to inactivation of the sodium channels with abolition of the inward sodium current.
• This is followed by a plateau in phase 2 in which continued slow calcium entry into the cell balances the electrical effect of potassium loss, as more voltage-dependent potassium channels open up. The voltage in the plateau phase is sufficient to maintain the sodium channels in the closed, inactive state.
• The cessation of the calcium current and a further increase in potassium current leads to rapid completion of repolarization with return to the resting potential (phase 3).
• Normal cell sodium and potassium activities are restored by the Na-K-ATPase pump, which extrudes the sodium that entered during depolarization and pumps in the potassium that was lost during repolarization.

The action potential at a specific region of membrane is conducted along the membrane and depolarizes neighboring regions, causing their thresholds to be reached, thereby generating another local action potential. This process conducts the action potential as an electrical signal along the muscle fibers of the heart. Linear propagation of the action potential occurs rapidly because the myocytes along muscle fibers are electrically continuous. An action potential can also cause the depolarization of a neighboring fiber, and the electrical impulse occurs as a "wave" through the heart.