Variability of spontaneous Ca2+ release between different rat ventricular myocytes is correlated with Na+-Ca2+ exchange and [Na+](i)

We have studied the factors responsible for the variation of the frequency of ''waves'' caused by spontaneous Ca2+ release in rat ventricular myocytes. The experiments were performed in isolated myocytes using the fluorescent indicators Indo-1 (to measure [Ca2+](i)) and SBFI (to measure [Na+](i)). After electrical stimulation (either with action potentials or voltage-clamp pulses), some cells showed spontaneous Ca2+ release. The frequency of this release, where present, was variable. The Ca2+ content of the sarcoplasmic reticulum (SR) was measured by applying caffeine (10 mmol/L). The resulting increase of [Ca2+](i) activated the electrogenic Na+-Ca2+ exchange, and the integral of this current was used to estimate the Ca2+ content of the SR. The SR Ca2+ content was significantly higher in cells that oscillated at high rates (>10 min(-1)) than in those that were quiescent. The rate of removal of Ca2+ from the cytoplasm by non-SR mechanisms was measured by adding caffeine (10 mmol/L) and measuring the rate constant of decay of the resulting increase of [Ca2+](i). Cells that had a high rate constant of decay of [Ca2+](i) had a low frequency of oscillations. Measurements of [Na+](i) showed a positive correlation between the frequency of spontaneous SR Ca2+ release and [Na+](i). After cessation of stimulation, there was a gradual decrease of [Na+](i), which was correlated with a parallel decrease of the frequency of oscillation rate. We conclude that the variability of frequency of spontaneous SR Ca2+ release is due to variations of the rare of Ca2+ removal from the cell, which are probably due to Na+-Ca2+ exchange. The variability of Na+ -Ca2+ exchange rate, in turn, is likely to result from variations of [Na+](i).