Effects of β2-adrenergic stimulation on single-channel gating of rat cardiac L-type Ca2+channels

Cardiac L-type Ca2+ channels can be stimulated by activation of beta2-adrenoceptors. We intended to determine how the gating behavior at the single-channel level (cell-attached configuration) is affected after selective stimulation of beta2-adrenoceptors. Rat cardiomyocytes were exposed to zinterol, a beta2-agonist (n = 7), isoproterenol (n = 6), a nonselective agonist, 8-bromo-cAMP (n = 6), and a combination of isoproterenol and ICI-118551 (n = 8), a selective beta2-receptor antagonist, or isoproterenol and CGP-20712A, a beta1-selective antagonist (n = 7). In all groups the ensemble-average current and the availability of the channels to open on depolarization were increased in a similar fashion. In addition, the open probability (Po) within active sweeps was elevated. However, zinterol exerted this effect in a unique manner. It elevated Po not by shortening closed times but solely by reducing active sweeps with very low Po and a short burst duration. All zinterol effects were abolished by ICI-118551 (n = 5) and mimicked by isoproterenol plus CGP-20712A (n = 7). We conclude that beta2-adrenoceptor activation of L-type channels differs qualitatively from the classical cAMP-dependent mechanism.