Unchanged beta-adrenergic stimulation of cardiac L-type calcium channels in Ca v 1.2 phosphorylation site S1928A mutant mice

J Biol Chem. 2008 Dec 12;283(50):34738-44. doi: 10.1074/jbc.M804981200. Epub 2008 Sep 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / chemistry
  • Animals
  • Calcium Channels, L-Type / chemistry
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Echocardiography
  • Electrophysiology
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Mutation
  • Myocytes, Cardiac / metabolism
  • Phosphorylation
  • Receptors, Adrenergic, beta / metabolism*
  • Serine / chemistry


  • Calcium Channels, L-Type
  • L-type calcium channel alpha(1C)
  • Receptors, Adrenergic, beta
  • Serine
  • Cyclic AMP-Dependent Protein Kinases
  • Alanine