Mechanisms of calcium accumulation and transport in cardiac relaxing system (sarcoplasmic reticulum membranes): Effects of Verapamil, D-600, X537A and A23187

Abstract

Verapamil and D-600, two potent ( I 50 = 10 −8 to 10 −7 m) calcium-dependent negative inotropic agents, are thought to act by decreasing calcium conductance (transmembrane calcium influx) across sarcolemmal membranes. These agents, although inhibiting cardiac relaxing system (sarcoplasmic reticulum fragments) calcium binding and uptake, did so at very high concentrations ( I 50 ∼ 1 m m) suggesting that their negative inotropic effect occurs by an action on a site other than the sarcoplasmic reticulum. The agents did not influence the rate of spontaneous release of calcium from cardiac relaxing system, nor did they affect the rapid release induced by a sudden increase in pH or by the addition of X537A or A23187, potent ionophoric agents that release calcium from sarcoplasmic reticulum fragments. The lack of effect on release suggests that “calcium channels” are not an important component of calcium release from cardiac relaxing system.