GTP-binding proteins mediate transmitter inhibition of voltage-dependent calcium channels.
The modulation of voltage-dependent calcium channels by hormones and neurotransmitters has important implications for the control of many Ca2+-dependent cellular functions including exocytosis and contractility. We made use of electrophysiological techniques, including whole-cell patch-clamp recordings from dorsal root ganglion (DRG) neurones, to demonstrate a role for GTP-binding proteins (G-proteins) as signal transducers in the noradrenaline- and gamma-aminobutyric acid (GABA)-induced inhibition of voltage-dependent calcium channels. This action of the transmitters was blocked by: (1) preincubation of the cells with pertussis toxin (a bacterial exotoxin catalysing ADP-ribosylation of G-proteins); or (2) intracellular administration of guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S), a non-hydrolysable analogue of GDP that competitively inhibits the binding of GTP to G-proteins. Our findings provide the first direct demonstration of the G-protein-mediated inhibition of voltage-dependent calcium channels by neurotransmitters. This mode of transmitter action may explain the ability of noradrenaline and GABA to presynaptically inhibit Ca2+-dependent neurosecretion from DRG sensory neurones.
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002642:Chick Embryo; D000242:Cyclic AMP / Q000502:physiology; D004075:Diglycerides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D005727:Ganglia, Spinal; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials; D009433:Neural Inhibition / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D004075:Diglycerides; D007473:Ion Channels; D018377:Neurotransmitter Agents; D010566:Virulence Factors, Bordetella; D005680:gamma-Aminobutyric Acid; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium; D009638:Norepinephrine