The beta-adrenergic cascade is important for the regulation of voltage-dependent Ca channels by phosphorylation. Here we report that isoproterenol (ISO) profoundly alters the voltage-dependent properties of L-type Ca channels studied in rat ventricular cells. ISO (1 microM) shifted both threshold and maximal activation of Ba current (IBa) towards more negative potentials (approx. 10 mV). An equivalent shift was observed in the steady-state voltage-dependent inactivation curve. As a consequence, the potentiation induced by ISO on IBa was greater for weak depolarizations and from negative holding potentials (Vh). We have excluded that the contribution of minor uncompensated series resistances, the activation of Cl currents or changes in junction potential during the experiments account for these effects. In addition, ISO had a dual effect on IBa decay depending on the voltage step (acceleration below, slowing above -10 mV). In conclusion, it is postulated that the voltage dependence of the potentiating effects of ISO on Ca channels activity may ensure a selective regulation among heart tissues with different membrane resting potentials.