Isoproterenol increased Ca2+ current amplitude dose-dependently (EC50 57.1 nM) in both wild-type and PLB-knockout mice, but only prolonged the rate of inactivation in PLB-knockout cells.
Phospholamban (PLB) ablation is associated with enhanced sarcoplasmic reticulum (SR) Ca2+ uptake and attenuation of the cardiac contractile responses to beta-adrenergic agonists. In the present study, we compared the effects of isoproterenol (Iso) on the Ca2+ currents (ICa) of ventricular myocytes isolated from wild-type (WT) and PLB knockout (PLB-KO) mice. Current density and voltage dependence of ICa were similar between WT and PLB-KO cells. However, ICa recorded from PLB-KO myocytes had significantly faster decay kinetics. Iso increased ICa amplitude in both groups in a dose-dependent manner (50% effective concentration, 57.1 nM). Iso did not alter the rate of ICa inactivation in WT cells but significantly prolonged the rate of inactivation in PLB-KO cells. When Ba2+ was used as the charge carrier, Iso slowed the decay of the current in both WT and PLB-KO cells. Depletion of SR Ca2+ by ryanodine also slowed the rate of inactivation of ICa, and subsequent application of Iso further reduced the inactivation rate of both groups. These results suggest that enhanced Ca2+ release from the SR offsets the slowing effects of beta-adrenergic receptor stimulation on the rate of inactivation of ICa.
Sako et al. (Sat,) reported a other. Isoproterenol vs. Wild-type (WT) mice was evaluated on Ca2+ currents (ICa) amplitude and inactivation rate. Isoproterenol increased Ca2+ current amplitude dose-dependently (EC50 57.1 nM) in both wild-type and PLB-knockout mice, but only prolonged the rate of inactivation in PLB-knockout cells.
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