Contribution of spontaneous L-type Ca2+ channel activation to the genesis of Ca2+ sparks in resting cardiac myocytes

摘要

Ca~(2+) sparks are the elementary events of intracellular Ca2+ release from the sar-coplasmic reticulum in cardiac myocytes. In order to investigate whether spontaneous L-type Ca~(2+) channel activation contributes to the genesis of spontaneous Ca~(2+) sparks, we used confocal laser scanning microscopy and fluo-4 to visualize local Ca~(2+) sparks in intact rat ventricular myocytes. In the presence of 0.2 mmol/L CdCI_2 which inhibits spontaneous L-type Ca~(2+) channel activation, the rate of occurrence of spontaneous Ca~(2+) sparks was halved from 4.20 to 2.04 events/(100 mu m centre dot s), with temporal and spatial properties of individual Ca~(2+) sparks unchanged. Analysis of the Cd~(2+)-sensitive spark production revealed an open probability of ~10~(-5) for L-type channels at the rest membrane potentials (-80 mV). Thus, infrequent and stochastic openings of sarcolemmal L-type Ca~(2+) channels in resting heart cells contribute significantly to the production of spontaneous Ca~(2+) sparks.