Enhancement of N- and L-type calcium channel currents by protein kinase C in frog sympathetic neurons.
The effect of protein kinase C (PKC) stimulation on Ca2+ channels was studied in frog sympathetic neurons. 12,13-Phorbol dibutyrate (PDBu) consistently augmented Ca2+ channel currents in whole-cell recordings. This enhancement was blocked by staurosporine and PKC(19-31), but not produced by 4 alpha-phorbol 12,13-didecanoate, indicating that PDBu acts via PKC. Both N- and L-type currents, as isolated pharmacologically, were increased. PKC enhancement was independent of the extent of G protein activation, indicating that it was not caused by removal of tonic G protein inhibition. In unitary recordings PDBu produced dramatic increases in single N- and L-type channel activity by sharply decreasing closed time intervals between adjacent openings, but did not alter the unitary current size or mean open time. This up-modulation by PKC may constitute a positive feedback mechanism in the regulation of neuronal Ca2+ channel activity.
Department of Molecular and Cellular Physiology, Stanford University, California 94305.
J
J
Yang
R W
RW
Tsien
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000502:physiology; D005728:Ganglia, Sympathetic / Q000502:physiology*; D007700:Kinetics; D009474:Neurons / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000494:pharmacology*; D011892:Rana catesbeiana; D019311:Staurosporine
D000470:Alkaloids; D015220:Calcium Channels; D010703:Phorbol Esters; C008876:phorbol-12,13-didecanoate; D001464:Barium; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D019311:Staurosporine