Jpn. J. Pharmacol. 81 (4), 324 - 331 (1999)

-Current Perspective-
Receptor-Mediated Modulation of Voltage-Dependent Ca2+ Channels
via Heterotrimeric G-proteins in Neurons

Shuji Kaneko1, Akinori Akaike2 and Masamichi Satoh3

Departments of 1Neuropharmacology, 2Pharmacology, and 3Molecular Pharmacology,
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606 - 8501, Japan

Abstract: The activity of voltage-dependent Ca2+ channels is highly regulated by neurotransmitter receptors coupled to heterotrimeric G-proteins. In the expression studies using cloned Ca2+ channel subunits, it has been clarified that the main mechanism of the inhibition of N-type channel current is mediated directly by G-protein subunits in a membrane-delimited and voltage-sensitive manner. In addition, recent studies have also clarified that N-type channels are modulated by several G-protein subunits in different ways. Among them, Go mediates a voltage-resistant inhibition of N-type current by neurotransmitters. This type of inhibition is more apparent in the case of P/Q-type channels in both native cells and expression systems. Moreover, other G-protein subunits, such as Gq and Gs, also seem to regulate N-type channels in a membrane-delimited manner. The fine tunings of Ca2+ channel activity by intracellular proteins have physiological and pathological meanings in the regulation of Ca2+ influx into excitable cells by neurotransmitters and pharmacological implications as novel drug targets for controlling Ca2+ influx.

Keywords: Voltage-dependent Ca2+ channel, GTP-binding protein, N-type, P/Q-type

Copyright The Japanese Pharmacological Society 1999

[Back to TOC]