Abstract: | Phospholamban(PLB) ablation is associated with enhanced sarcoplasmic reticulum (SR)Ca2+ uptake and attenuation of thecardiac contractile responses to -adrenergic agonists. In thepresent study, we compared the effects of isoproterenol (Iso) on theCa2+ currents(ICa) ofventricular myocytes isolated from wild-type (WT) and PLB knockout(PLB-KO) mice. Current density and voltage dependence ofICa were similarbetween WT and PLB-KO cells. However, ICa recorded fromPLB-KO myocytes had significantly faster decay kinetics. Iso increasedICa amplitude inboth groups in a dose-dependent manner (50% effective concentration,57.1 nM). Iso did not alter the rate ofICa inactivationin WT cells but significantly prolonged the rate of inactivation inPLB-KO cells. When Ba2+ was usedas the charge carrier, Iso slowed the decay of the current in both WTand PLB-KO cells. Depletion of SRCa2+ by ryanodine also slowed therate of inactivation ofICa, and subsequent application of Iso further reduced the inactivation rate ofboth groups. These results suggest that enhancedCa2+ release from the SR offsetsthe slowing effects of -adrenergic receptor stimulation on the rateof inactivation ofICa. |