title: Beta-adrenergic stimulation of L-type Ca2+ channels in cardiac myocytes requires the distal carboxyl terminus of alpha1C but not serine 1928.
abstract: Beta-adrenoceptor stimulation robustly increases cardiac L-type Ca2+ current (ICaL); 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 alpha1C 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 alpha1C 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 alpha1C adenoviruses, coexpressed with beta2 subunits. Expression of alpha1C 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 alpha1C 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.
authors.affiliation: Institute of Molecular Cardiobiology, The Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Anand N
authors.initials: AN
authors.lastname: Ganesan
authors.forename: Christoph
authors.initials: C
authors.lastname: Maack
authors.forename: David C
authors.initials: DC
authors.lastname: Johns
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sidor
authors.forename: Brian
authors.initials: B
authors.lastname: O'Rourke
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D021122:Protein Subunits; D011943:Receptors, Adrenergic, beta / Q000737:chemistry* / Q000502:physiology*; D012694:Serine
chemical_list: D020746:Calcium Channels, L-Type; D021122:Protein Subunits; D011943:Receptors, Adrenergic, beta; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol