Receptor-mediated modulation of voltage-dependent Ca2+ channels via heterotrimeric G-proteins in neurons.
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 betagamma 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 alpha subunits in different ways. Among them, G(alpha 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 G(alpha q) and G(alpha 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.
Kaneko
S
S
Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Akaike
A
A
Satoh
M
M
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D015220:Calcium Channels; D017981:Receptors, Neurotransmitter; D019204:GTP-Binding Proteins