Lack of involvement of protein kinase A phosphorylation in voltage-dependent facilitation of the activity of human cardiac L-type calcium channels

Biochem Biophys Res Commun. 1996 Apr 16;221(2):446-53. doi: 10.1006/bbrc.1996.0615.


Phosphorylation by protein kinase A is thought to be involved in voltage-dependent facilitation of calcium channels. Here we have shown that the subunit complex of a cloned human cardiac calcium channel, expressed in Xenopus oocytes, responds to voltage-dependent facilitation by an approximately 50% increase of the calcium channel peak current. The removal of all protein kinase A consensus sequences by site-directed mutagenesis decreased but did not eliminate the response to prepulse facilitation. Moreover, Rp-cAMP-S, an inhibitor of protein kinase A, could not prevent facilitation of the wild-type calcium channel currents. Similarly, AMP-PNP a nonhydrolyzable analog of ATP, while significantly decreasing the whole-cell current amplitude, failed to reduce the response to double-pulse facilitation. Therefore, we conclude that the voltage-dependent facilitation of cloned calcium channel currents is not due to enhancement of phosphorylation, but probably to some type of voltage-induced conformational change in the channel.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Imidodiphosphate / pharmacology
  • Animals
  • Calcium Channels / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Female
  • Humans
  • Ion Channel Gating*
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Phosphorylation
  • Xenopus laevis


  • Calcium Channels
  • Adenylyl Imidodiphosphate
  • Cyclic AMP-Dependent Protein Kinases