Tonic inhibition and rebound facilitation of a neuronal calcium channel by a GTP-binding protein.

AUTOR(ES)

Kasai, H

RESUMO

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.

Documentos Relacionados

• Voltage- and time-dependent inhibition of neuronal calcium channels by a GTP-binding protein in a mammalian cell line.
• GTP-binding protein βγ subunits mediate presynaptic calcium current inhibition by GABAB receptor
• Nucleotide sequence of the mouse ypt1 gene encoding a ras-related GTP-binding protein.
• Activation of phospholipase C beta 2 by the alpha and beta gamma subunits of trimeric GTP-binding protein.
• Exchange of guanine nucleotide between GTP-binding proteins that regulate neuronal adenylate cyclase.