Modulation of Ca2+ channels by protein kinase C in rat central and peripheral neurons: disruption of G protein-mediated inhibition.
Activation of protein kinase C (PKC) reduced G protein-dependent inhibition of Ca2+ channels by glutamate, GA-BAB, adenosine, muscarinic, alpha-adrenergic, and LHRH receptors in a variety of central and peripheral neurons. PKC stimulation also relieved the inhibitory effect of internal GTP gamma S and reduced tonic G protein-mediated inhibition observed with internal GTP in the absence of transmitter receptor agonist. Basal Ca2+ channel currents were enhanced by PKC stimulation in most neurons studied. The PKC-induced enhancement of basal current was voltage dependent, and enhanced currents displayed altered kinetics. Inhibition of G proteins with GDP beta S attenuated the PKC-induced enhancement of basal Ca2+ channel current. These results show that PKC regulates the inhibitory effects of G proteins, possibly by disrupting the coupling of G proteins to Ca2+ channels. The PKC-induced enhancement of Ca2+ channel current results, at least in part, from the removal of tonic G protein-mediated inhibition.
Swartz
K J
KJ
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010525:Peripheral Nerves / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000494:pharmacology*; D051381:Rats
D015220:Calcium Channels; D018377:Neurotransmitter Agents; D011493:Protein Kinase C; D019204:GTP-Binding Proteins