Determinants of PKC-dependent modulation of a family of neuronal calcium channels.
The modulation of Ca2+ channel activity by protein kinases contributes to the dynamic regulation of neuronal physiology. Using the transient expression of a family of neuronal Ca2+ channels, we have identified several factors that contribute to the PKC-dependent modulation of Ca2+ channels. First, the nature of the Ca2+ channel alpha 1 subunit protein is critical. Both alpha 1B and alpha 1E channels exhibit a 30%-40% increase in peak currents after exposure to phorbol esters, whereas neither alpha 1A nor alpha 1C channels are significantly affected. This up-regulation can be mimicked for alpha 1E channels by stimulation of a coexpressed metabotropic glutamate receptor (type 1 alpha) through a PKC-dependent pathway. Second, PKC-stimulated up-regulation is dependent upon coexpression with a Ca2+ channel beta subunit. Third, substitution of the cytoplasmic domain I-II linker from alpha 1B confers PKC sensitivity to alpha 1A channels. The results provide direct evidence for the modulation of a subset of neuronal Ca2+ channels by PKC and implicate alpha 1 and beta subunit interactions in regulating channel activity via second messenger pathways.
Stea
A
A
Department of Neuroscience, University of British Columbia, Vancouver, Canada.
Soong
T W
TW
Snutch
T P
TP
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D007202:Indicators and Reagents; D007700:Kinetics; D046911:Macromolecular Substances; D009474:Neurons / Q000502:physiology*; D009865:Oocytes / Q000502:physiology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D015290:Second Messenger Systems; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014982:Xenopus laevis
D015220:Calcium Channels; D007202:Indicators and Reagents; D046911:Macromolecular Substances; D018094:Receptors, Metabotropic Glutamate; D010566:Virulence Factors, Bordetella; D015240:Phorbol 12,13-Dibutyrate; D004533:Egtazic Acid; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium