G-PROTEIN MODULATION OF ION PERMEATION THROUGH N-TYPE CALCIUM CHANNELS

N-TYPE calcium channels in cell membranes are inhibited by neurotransmitters such as noradrenaline1-4, luteinizing hormone-releasing (LHRH)5-7, gamma-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 bow 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-gammaS than was current carried by Ba2+. With external Ba2+ and internal Cs+, LHRH inhibited the Ba2+-carried inward limb of the instantaneous current-voltage curve much more than the Cs+-carried outward limb. Noise analysis showed that LHRH or GTP-gammaS 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.