Since information is lacking regarding how the enhancement of net sarcoplasmic reticulum (SR) Ca²⁺ uptake may affect cardiac electrophysiological properties in vivo, we analyzed it with caldaret which can decrease SR Ca²⁺ leak, enhance SR Ca²⁺ reuptake and inhibit reverse-mode Na⁺/Ca²⁺ exchanger. Caldaret in doses of 0.5, 5 and 50 µg/kg was intravenously administered over 10 min to the halothane-anesthetized beagle dogs (n=4), possibly providing pharmacologically effective plasma concentration. The low and middle doses increased the ventricular contraction, which can be explained by its on-target pharmacological activities. The high dose enhanced the sinus automaticity followed by its suppression in addition to the increase of the total peripheral resistance. The low and middle doses enhanced the atrioventricular conduction. The middle and high doses prolonged the ventricular effective refractory period without altering the intraventricular conduction or repolarization period. Thus, modulation of intracellular Ca²⁺ handling by caldaret can induce not only inotropic effect, but also various electrophysiological actions on the in situ heart.