Positive inotropic and chronotropic effects of the calcium ionophore A23187 (calimycin) on guinea-pig atria.

The inotropic and chronotropic effects of the calcium ionophore A23187 (calimycin = CA) in isolated, superfused, electrically driven, auxotonically contracting left and spontaneously beating right guinea-pig atria were examined at different Ca2+ concentrations. 10(-6) to 10(-5) mol/l CA shows significantly positive inotropic and chronotropic effects. The inotropic effect of CA can be significantly diminished by relatively high concentrations of Ca2+ channel antagonists and relatively low concentrations of ryanodine. The positive chronotropic effect of CA can be reduced slightly, but significantly, by beta-adrenoceptor antagonists and histamine H2-receptor antagonists. From this we infer that the positive inotropic effect of CA is mainly due to the release of Ca2+ from cardiac sarcoplasmic reticulum, whereas catecholamine and histamine release appear to contribute to the positive chronotropic effect of the ionophore.