Effect of extracellular calcium on contractile activation in guinea-pig ventricular muscle

The problem of whether or not the alterations in twitch tension of mammalian cardiac muscle induced by changes in extracellular Ca concentration ([Ca]o) are due to the Na-Ca exchange process across the surface membrane and/or the changes in the amount of Ca in the sarcoplasmic reticulum has been re-examined by using thin bundles (70-120 micron diameter) dissected from guinea-pig papillary muscle. The observed time course of the change in the twitch tension due to a step change in [Ca]o was compared with that computed on a basis of the diffusion process of Ca ions in a circular cylinder and of the steady-state relation between [Ca]o and twitch tension. After a sudden decrease in [Ca]o from 2 mM to various lower concentrations, the isometric twitch tension of the thin bundles first fell rapidly and monotonically and then showed a much smaller and slower secondary fall. The correspondence of the observed time course of the rapid phase with the predicted time course and the observed half-time of the rapid phase ranging from 1.0 to 2.5 s indicate that the rapidity of the twitch response may be dominated by simple diffusion of Ca ions through the extracellular space. If so, the effective diffusion constant of Ca ions inside the bundles was 1.4 +/- 0.2 X 10(-6) cm2/s (mean +/- S.E., n = 9). The magnitude and direction of the step change in [Ca]o or the change at different stimulus frequencies gave rise to dissimilar time courses of the contractile change; the difference in the rapid time courses due to these factors could be explained by the simple diffusion models, but not in the much slower phase. The half-time for the Ca effect was the same as that for the rapid effect of Na ions in the external solutions. The time course of twitch decline due to [Ca]o decrease in the Na-free (Li) solution was identical to that predicted from the time course measured in the Na-rich solution and the steady-state relation between [Ca]o and tension in the Na-free solution. The half-time of Ca leak from the sarcoplasmic reticulum in the skinned cardiac muscle was 40-60 s in the presence of 10 mM-EGTA, much shorter than that of the Ca leak in the skinned amphibian skeletal muscle, but much longer than that of twitch responses due to step changes in [Ca]o in the intact cardiac muscle.(ABSTRACT TRUNCATED AT 400 WORDS)