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G-protein modulation of ion permeation through N-type calcium channels

Abstract

N-TYPE calcium channels in cell membranes are inhibited by neuro-transmitters such as noradrenaline1—4, luteinizing hormone-releas-ing hormone (LHRH)5—7, y-aminobutyric acid (GABA)8,9 and glutamate10,11. Although GTP-binding proteins (G proteins) are probably the common mediators of such inhibition6, 11—14, it is unclear exactly how G proteins alter the operation of the channel. Various experiments have shown changes in channel gating2—6,15,16. Here we show that inward current carried by Na+ through N-type channels was far less inhibited by LHRH or by internal GTP-γS than was current carried by Ba2+ . With external Ba2+ and internal Cs+, LHRH inhibited the Ba2+-carried inward limb of the instan-taneous current-voltage curve much more than the Cs+-carried outward limb. Noise analysis showed that LHRH or GTP-γS decrease single-channel current carried by Ba2+. These results suggest that alteration of the ion permeation pathway contributes significantly to G-protein inhibition of N-type Ca2+ channels.

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Kuo, CC., Bean, B. G-protein modulation of ion permeation through N-type calcium channels. Nature 365, 258–262 (1993). https://doi.org/10.1038/365258a0

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