β2-Adrenergic receptor agonists stimulate L-type calcium current independent of PKA in newborn rabbit ventricular myocytes

Selective stimulation of β2-adrenergic receptors (ARs) in newborn rabbit ventricular myocardium invokes a positive inotropic effect that is lost during postnatal maturation. The underlying mechanisms for this age-related stimulatory response remain unresolved. We examined the effects of β2-AR stimulation on L-type Ca2+ current (ICa,L) during postnatal development. ICa,L was measured (37°C; either Ca2+ or Ba2+ as the charge carrier) using the whole-cell patch-clamp technique in newborn (1 to 5 days old) and adult rabbit ventricular myocytes. Ca2+ transients were measured concomitantly by dialyzing the cell with indo-1. Activation of β2-ARs (with either 100 nM zinterol or 1 μM isoproterenol in the presence of the β1-AR antagonist, CGP20712A) stimulated ICa,L twofold in newborns but not in adults. The β2-AR-mediated increase in Ca2+ transient amplitude in newborns was due exclusively to the augmentation of ICa,L. Zinterol increased the rate of inactivation of ICa,L and increased the Ca2+ flux integral. The β...