Tonic inhibition and rebound facilitation of a neuronal calcium channel by a GTP-binding protein.
A significant fraction of differentiated NG108-15 neuroblastoma/glioma cells have Ca2+ channel current different from that of undifferentiated cells. In the former cells, the Ca2+ channel sensitive to omega-conotoxin GVIA had slowed activation kinetics and was facilitated by depolarizing prepulses. These kinetic features are identical to those produced by inhibition of the channel by G proteins. Prolonged treatment with prostaglandin E1 and theophylline, agents that cause cellular differentiation, promoted incidence and extent of the tonic inhibition. Intracellular guanosine 5'-[beta-thio]diphosphate removed the tonic inhibition, suggesting sustained activation of a G protein, but pertussis toxin did not block it. A sulfhydryl alkylating agent, N-ethylmaleimide (0.1 mM), rapidly eliminated agonist-induced inhibition, whereas N-ethylmaleimide spared the tonic inhibition and the one induced by intracellular guanosine 5'-[gamma-thio]triphosphate. An agonist could further inhibit the Ca2+ channel that was already tonically inhibited. After washout of an inhibitory agonist, the tonic inhibition was temporarily removed. This "rebound facilitation" gradually faded within a few minutes. Pertussis toxin or N-ethylmaleimide prevented the rebound facilitation, whereas phorbol ester, forskolin, or arachidonic acid induced neither the rebound facilitation nor the tonic inhibition. Whatever its mechanism, the tonic inhibition of Ca2+ channels may serve as the basis for long-term and bidirectional regulation of activity of neuronal Ca2+ channels.
Kasai
H
H
Abteilung Membranbiophysik, Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Federal Republic of Germany.
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials; D008978:Mollusk Venoms / Q000494:pharmacology; D009447:Neuroblastoma; D009474:Neurons / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D004745:Enkephalins; D008978:Mollusk Venoms; D010456:Peptides, Cyclic; D010566:Virulence Factors, Bordetella; D020881:Enkephalin, D-Penicillamine (2,5)-; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D005033:Ethylmaleimide