β-Adrenergic Stimulation of L-type Ca2+ Channels in Cardiac Myocytes Requires the Distal Carboxyl Terminus of α1C but Not Serine 1928

β-Adrenoceptor stimulation robustly increases cardiac L-type Ca 2+ 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 α 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 α 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 α 1C adenoviruses, coexpressed with β 2 subunits. Expression of α 1C truncated at 1905 dramatically attenuated the increase of peak I CaL induced by isoproterenol. However, the point mutation S1928A did not significantly attenuate the β-adrenergic response. The findings indicate that the distal carboxyl-terminus of α 1C plays an important role in β-adrenergic upregulation of cardiac L-type Ca 2+ channels, but that phosphorylation of serine 1928 is not required for this effect.