GTP-binding proteins mediate transmitter inhibition of voltage-dependent calcium channels

Nature. 1986 Feb 20-26;319(6055):670-2. doi: 10.1038/319670a0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Calcium / physiology*
  • Chick Embryo
  • Cyclic AMP / physiology
  • Diglycerides / pharmacology
  • GTP-Binding Proteins / antagonists & inhibitors
  • GTP-Binding Proteins / physiology*
  • Ganglia, Spinal
  • Ion Channels / physiology*
  • Membrane Potentials
  • Neural Inhibition* / drug effects
  • Neurotransmitter Agents / physiology*
  • Norepinephrine / physiology
  • Pertussis Toxin
  • Virulence Factors, Bordetella / pharmacology
  • gamma-Aminobutyric Acid / physiology

Substances

  • Diglycerides
  • Ion Channels
  • Neurotransmitter Agents
  • Virulence Factors, Bordetella
  • gamma-Aminobutyric Acid
  • Cyclic AMP
  • Pertussis Toxin
  • GTP-Binding Proteins
  • Calcium
  • Norepinephrine