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

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Abstract
N-type calcium channels in cell membranes are inhibited by neurotransmitters such as noradrenaline, luteinizing hormone-releasing hormone (LHRH), gamma-aminobutyric acid (GABA) and glutamate. Although GTP-binding proteins (G proteins) are probably the common mediators of such inhibition, it is unclear exactly how G proteins alter the operation of the channel. Various experiments have shown changes in channel gating. Here we show that inward current carried by Na+ through N-type channels was far less inhibited by LHRH or by internal GTP-gamma S than was current carried by Ba2+. With external Ba2+ and internal Cs+, LHRH inhibited the Ba(2+)-carried inward limb of the instantaneous current-voltage curve much more than the Cs(+)-carried outward limb. Noise analysis showed that LHRH or GTP-gamma S 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.