Ca influx and sarcoplasmic reticulum Ca release in cardiac muscle activation during postrest recovery

Abstract

The recovery of twitch tension (T) and Ca influx after 5-s to 10-min rest intervals was studied in rabbit, rat, and frog cardiac muscle. Extracellular double-barreled Ca-selective microelectrodes were used to assess transsarcolemmal Ca influx. In rabbit ventricle, T at the first postrest beat (B1) exceeded T at the second beat (B2). T and Ca influx then increase toward steady state in a parallel fashion. Since Ca influx is small at B1, this beat may be more dependent on Ca stored in the sarcoplasmic reticulum (SR), and subsequent beats may more closely reflect Ca influx. We have examined this hypothesis using agents that may preferentially inhibit either SR Ca release or Ca influx. SR inhibitors caffeine (5 mM) and ryanodine (100 nM) changed the pattern of T recovery so that B1 was now less than B2 and more closely paralleled the recovery of Ca influx. Caffeine and ryanodine decreased steady-state T to 89 +/- 9 and 78 +/- 3%, respectively. In contrast, B1 was found to be less susceptible to inhibition than B2 when exposed to La or Co (influx inhibitors). These results are consistent with a rabbit ventricle model in which the SR Ca release contributes greatly to B1, the SR contribution declines while the Ca influx component increases, and Ca influx at steady state can account for a large fraction of steady-state T. In adult rat ventricle, caffeine and ryanodine decrease steady-state T to 33 +/- 2 and 13 +/- 3%, respectively, changing the T recovery pattern from a monotonic decrease to a monotonic increase. These results are consistent with a model qualitatively the same as rabbit ventricle. However, the SR can account for most of steady-state T in the rat, and thus its decaying characteristic dominates the control postrest recovery. By inhibition of SR Ca release, the increasing component ascribed to Ca influx becomes apparent. Similar experiments were done to establish an order of relative dependence on SR Ca release: adult rat ventricle greater than rabbit atrium greater than rabbit ventricle greater than frog ventricle.