Cs+ inhibits spontaneous Ca2+ release from sarcoplasmic reticulum of skinned cardiac myocytes

Abstract

The effect of Cs+ on the function of the cardiac sarcoplasmic reticulum (SR) has been investigated in skinned cardiac myocytes. Isolated rat ventricular myocytes were permeabilized using saponin and then perfused with a solution containing 150 nmol/l Ca2+ and 10 μmol/l fura 2. Fura 2 fluorescence from the skinned cell was monitored to assess SR Ca2+ release. The frequency of spontaneous Ca2+ release from the SR decreased when K+ in the bathing solution was completely replaced with Cs+. Cs+ had little effect on the amplitude of spontaneous release but prolonged both the rise time and decay time. The SR Ca2+ content, assessed by application of caffeine, was reduced in the Cs+ solution. Cyclopiazonic acid produced effects similar to those of Cs+. Extracellular Cs+ (20 mmol/l) increased the amplitude of the Ca2+ transient and the SR Ca2+ content in intact field-stimulated cells but had little effect on the Ca2+ transient when the amplitude and duration of depolarization were kept constant using voltage clamp. These data suggest that Cs+ slows Ca2+ movement across the SR membrane, possibly by blocking the SR K+ channel, but has additional effects in intact cells that overcome its inhibitory effects on the SR.