Can strontium replace calcium as an activator of internal calcium release in cardiac muscles?: Study on a dual action of A23187

Abstract

The positive inotropic effect of A23187 has previously been indicated to be attributed to both the enhancement of the slow Ca inward current and the facilitation of Ca release from internal stores. The electromechanical effects of replacing external Ca by Sr on this dual action of A23187 were examined on guinea-pig papillary muscles driven at 0.2 Hz. Replacing most of external Ca by Sr (Sr 2.5 mM plus Ca 0.2 mM) (Sr-medium) increased the developed tension. This procedure simultaneously prolonged the time to peak developed tension (tPT) and the action potential duration at all repolarization phases (APD 10, APD 30 and ADP 80). In such preparations, A23187 (10(-6) M) caused a marked positive inotropic effect (938 +/- 180% of control) accompanied by a prolongation of APD at an early repolarization phase (APD 10), but did not affect tPT. Thereafter, returning superfusate to normal Ca medium (Ca 1.2 mM) in the presence of A23187 also caused a positive inotropic effect, but markedly shortened tPT. The electrical and mechanical responses to A23187 in Sr-medium were completely blocked by nifedipine (2 X 10(-6) M), Ca-channel-blocker, while the positive inotropic effect in normal Ca medium was not blocked by nifedipine. Ryanodine, an inhibitor of internal Ca release, did not affect the positive inotropic effect of A23187 in Sr-medium. These results suggest that in Sr-medium, an internal Ca pool of the myocardium, most likely sarcoplasmic reticulum, does not play a role in the activation of contraction.