G-protein modulation of ion permeation through N-type calcium channels.
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.
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
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D000818:Animals; D001464:Barium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002586:Cesium / Q000378:metabolism; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007477:Ions; D009474:Neurons / Q000378:metabolism; D011892:Rana catesbeiana; D012964:Sodium / Q000378:metabolism
D015220:Calcium Channels; D007477:Ions; D002586:Cesium; D001464:Barium; D007987:Gonadotropin-Releasing Hormone; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D012964:Sodium; D019204:GTP-Binding Proteins