title: Unchanged beta-adrenergic stimulation of cardiac L-type calcium channels in Ca v 1.2 phosphorylation site S1928A mutant mice.
abstract: Phosphorylation of serine 1928 (Ser(1928)) of the cardiac Ca(v)1.2 subunit of L-type Ca(2+) channels has been proposed as the mechanism for regulation of L-type Ca(2+) channels by protein kinase A (PKA). To test this directly in vivo, we generated a knock-in mouse with targeted mutation of Ser(1928) to alanine. This mutation did not affect basal L-type current characteristics or regulation of the L-type current by PKA and the beta-adrenergic receptor, whereas the mutation abolished phosphorylation of Ca(v)1.2 by PKA. Therefore, our data show that PKA phosphorylation of Ser(1928) of Ca(v)1.2 is not functionally involved in beta-adrenergic stimulation of Ca(v)1.2-mediated Ca(2+) influx into the cardiomyocyte.
authors.affiliation: Institut für Pharmakologie, Technische Universität München, Biedersteiner Strasse 29, 80802 München, Germany.
authors.forename: Toni
authors.initials: T
authors.lastname: Lemke
authors.forename: Andrea
authors.initials: A
authors.lastname: Welling
authors.forename: Carl Johannes
authors.initials: CJ
authors.lastname: Christel
authors.forename: Anne
authors.initials: A
authors.lastname: Blaich
authors.forename: Dominik
authors.initials: D
authors.lastname: Bernhard
authors.forename: Peter
authors.initials: P
authors.lastname: Lenhardt
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.forename: Sven
authors.initials: S
authors.lastname: Moosmang
mesh_terms: D000409:Alanine / Q000737:chemistry; D000818:Animals; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004452:Echocardiography; D004594:Electrophysiology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism; D010766:Phosphorylation; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012694:Serine / Q000737:chemistry
chemical_list: D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); D011943:Receptors, Adrenergic, beta; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases; D000409:Alanine