Contribution of Sarcoplasmic Reticulum Ca2|[plus]| Release and Ca2|[plus]| Transporters on Sarcolemmal Channels to Ca2|[plus]| Transient in Fetal Mouse Heart

摘要

Sarcoplasmic reticulum (SR) Ca2+ release has been shown not to be the predominant mechanism responsible for excitation-contraction (E-C) coupling in fetal myocytes. However, most of the studies have been conducted either on primary cultures or acutely isolated cells, in which an apparent reduction of ryanodine receptor density have been reported. We aimed to elucidate the contribution of SR Ca2+ release and Ca2+ transporters on sarcolemmal channels to Ca2+ transients in fetal mouse whole hearts. On embryonic day 13.5, ryanodine significantly reduced the amplitude of the Ca2+ transient to 27.2 ± 4.4% of the control, and both nickel and SEA0400 significantly prolonged the time to peak from 84 ± 2 ms to 140 ± 5 ms and 129 ± 6 ms, respectively, whereas nifedipine did not alter it. Therefore, at early fetal stages, SR Ca2+ release should be an important component of E-C coupling, and T-type Ca2+ channel and reverse mode sodium-calcium exchanger (NCX)-mediated SR Ca2+ release could be the predominant contributors. Using embryonic mouse cultured cardiomyocytes, we showed that both nifedipine and nickel inhibited the ability of NCX to extrude Ca2+ from the cytosol. From these results, we propose a novel idea concerning E-C coupling in immature heart.Abbreviations: AP, action potential; CICR, calcium-induced calcium release; E-C, excitation-contraction; ED, embryonic day; LCC, L-type Ca2+ channel; NCX, sodium-calcium exchanger; RyR, ryanodine receptor; SR, sarcoplasmic reticulum; TCC, T-type Ca2+ channel; TTP, time to peak; T50, time to 50% relaxation