β-adrenergic stimulation of L-type Ca2+ channels in cardiac myocytes requires the distal carboxyl terminus of α1C but not serine 1928

beta-Adrenoceptor stimulation robustly increases cardiac L-type Ca2+ current (I-CaL); yet the molecular mechanism of this effect is still not well understood. Previous reports have shown in vitro phosphorylation of a consensus protein kinase A site at serine 1928 on the carboxyl terminus of the alpha(1C) subunit; however, the functional role of this site has not been investigated in cardiac myocytes. Here, we examine the effects of truncating the distal carboxyl terminus of the alpha(1C) subunit at amino acid residue 1905 or mutating the putative protein kinase A site at serine 1928 to alanine in adult guinea pig myocytes, using novel dihydropyridine-insensitive alpha(1C) adenoviruses, coexpressed with beta(2) subunits. Expression of alpha(1C) truncated at 1905 dramatically attenuated the increase of peak ICaL induced by isoproterenol. However, the point mutation S1928A did not significantly attenuate the beta-adrenergic response. The findings indicate that the distal carboxyl-terminus of alpha(1C) plays an important role in beta-adrenergic upregulation of cardiac L-type Ca2+-channels, but that phosphorylation of serine 1928 is not required for this effect.