Excitation-contraction coupling in myocardium: implications of calcium release and Na+-Ca2+ exchange

In this paper, we present evidence in support of the hypothesis that electrogenic Na+-Ca2+ exchange is responsible for three phenomena in rat cardiac muscle: the slow repolarization phase of the action potential, the time course of the mechanical recovery process, and the development of triggered arrhythmias. It was shown that the duration of the slow phase of repolarization of the action potential varies in proportion to the Na+ concentration gradient and inversely with the Ca2+ concentration gradient over the cell membrane. This suggested that Na+-Ca2+ exchange can generate a current of sufficient magnitude to maintain the membrane depolarized at a level of -60 mV. The mechanical restitution process of rat cardiac trabeculae was shown to exhibit three phase. The first phase, alpha, probably reflects rapid transport of calcium in the sarcoplasmic reticulum from the uptake sites to the release sites. After the initial increase of force during alpha, force rises further during phase beta and then declines during phase gamma. During all phases, force increases with the extracellular calcium concentration. beta is accelerated by preceding extrasystoles, while an increase of the heart rate causes force to increase at approximately the same rate but to a higher level during phase beta. These observations are compatible with a model in which the sarcoplasmic reticulum sequesters calcium from the cytosol, while the membrane of the sarcoplasmic reticulum is assumed to exhibit also a small leak of calcium into the cytosol.(ABSTRACT TRUNCATED AT 250 WORDS)