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 ƒÀƒÁ 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 ƒ¿ subunits in different ways. Among them, Gƒ¿o 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 Gƒ¿q and Gƒ¿s, 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