Cs1 inhibits spontaneous Ca21 release from sarcoplasmic reticulum of skinned cardiac myocytes

Kawai, Makoto, Munir Hussain, and Clive H. Orchard. Cs1 inhibits spontaneous Ca21 release from sarcoplasmic reticulum of skinned cardiac myocytes. Am. J. Physiol. 275 (Heart Circ. Physiol. 44): H422–H430, 1998.—The effect of Cs1 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 Ca21 and 10 μmol/l fura 2. Fura 2 fluorescence from the skinned cell was monitored to assess SR Ca21 release. The frequency of spontaneous Ca21 release from the SR decreased when K1 in the bathing solution was completely replaced with Cs1. Cs1 had little effect on the amplitude of spontaneous release but prolonged both the rise time and decay time. The SR Ca21 content, assessed by application of caffeine, was reduced in the Cs1 solution. Cyclopiazonic acid produced effects similar to those of Cs1. Extracellular Cs1 (20 mmol/l) increased the amplitude of the Ca21 transient and the SR Ca21 content in intact field-stimulated cells but had little effect on the Ca21 transient when the amplitude and duration of depolarization were kept constant using voltage clamp. These data suggest that Cs1 slows Ca21 movement across the SR membrane, possibly by blocking the SR K1 channel, but has additional effects in intact cells that overcome its inhibitory effects on the SR.