Unchanged beta-adrenergic stimulation of cardiac L-type calcium channels in Ca v 1.2 phosphorylation site S1928A mutant mice.
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.
Lemke
Toni
T
Institut für Pharmakologie, Technische Universität München, Biedersteiner Strasse 29, 80802 München, Germany.
Welling
Andrea
A
Christel
Carl Johannes
CJ
Blaich
Anne
A
Bernhard
Dominik
D
Lenhardt
Peter
P
Hofmann
Franz
F
Moosmang
Sven
S
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
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