Me. Diaz et al., VARIABILITY OF SPONTANEOUS CA2-CA2+ EXCHANGE AND [NA+](I)( RELEASE BETWEEN DIFFERENT RAT VENTRICULAR MYOCYTES IS CORRELATED WITH NA+), Circulation research, 78(5), 1996, pp. 857-862
We have studied the factors responsible for the variation of the frequ
ency of ''waves'' caused by spontaneous Ca2+ release in rat ventricula
r 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 po
tentials or voltage-clamp pulses), some cells showed spontaneous Ca2release. The frequency of this release, where present, was variable. T
he Ca2+ content of the sarcoplasmic reticulum (SR) was measured by app
lying caffeine (10 mmol/L). The resulting increase of [Ca2+](i) activa
ted the electrogenic Na+-Ca2+ exchange, and the integral of this curre
nt was used to estimate the Ca2+ content of the SR. The SR Ca2+ conten
t was significantly higher in cells that oscillated at high rates (>10
min(-1)) than in those that were quiescent. The rate of removal of Ca
2+ from the cytoplasm by non-SR mechanisms was measured by adding caff
eine (10 mmol/L) and measuring the rate constant of decay of the resul
ting increase of [Ca2+](i). Cells that had a high rate constant of dec
ay of [Ca2+](i) had a low frequency of oscillations. Measurements of [
Na+](i) showed a positive correlation between the frequency of spontan
eous SR Ca2+ release and [Na+](i). After cessation of stimulation, the
re was a gradual decrease of [Na+](i), which was correlated with a par
allel 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 probab
ly due to Na+-Ca2+ exchange. The variability of Na+ -Ca2+ exchange rat
e, in turn, is likely to result from variations of [Na+](i).