Enhanced Ca 2+ Current and Decreased Ca 2+ Efflux Restore Sarcoplasmic Reticulum Ca 2+ Content After Depletion

Abstract Ca 2+ i was measured using the fluorescent indicator indo 1 in voltage-clamped ferret and rat ventricular myocytes. The Ca 2+ content of the sarcoplasmic reticulum (SR) was estimated from the integral of the Na + -Ca 2+ exchange current activated by caffeine. Refilling of the SR after caffeine removal was enhanced by stimulation. As the systolic Ca 2+ transient recovered, the integral of the L-type Ca 2+ current decreased and that of the Na + -Ca 2+ exchange tail current increased. For the early pulses, the gain of Ca 2+ via the Ca 2+ current is greater than the loss via the exchanger, and during steady state stimulation, the fluxes are equal. The difference in the integrals gives a measure of the net gain of cell Ca 2+ with each pulse. When these are summed, the calculated gain of cell Ca 2+ agrees well with the increase of SR Ca 2+ produced by stimulation, as measured from the caffeine-evoked currents. There was a nonlinear relationship between SR Ca 2+ content and the magnitude of the systolic Ca 2+ transient such that at high SR Ca 2+ content a given increase of content had a greater effect on the Ca 2+ transient than did an increase at low SR content. In conclusion, the effects of systolic Ca 2+ on the Ca 2+ current and Na + -Ca 2+ exchange current provide a means to regulate SR Ca 2+ content and thence the systolic Ca 2+ transient.