Voltage-dependent modulation of N-type calcium channels by G-protein beta gamma subunits

Nature. 1996 Mar 21;380(6571):255-8. doi: 10.1038/380255a0.


The most commonly used signal transduction pathway for receptor-mediated N-type Ca2+-channel modulation involves activation of a heterotrimeric G protein to produce voltage-dependent inhibition. Although it is widely assumed that Galpha mediates this effect, experiments to address this hypothesis directly are lacking. Here I show that transient overexpression of Gbetagamma in sympathetic neurons mimics and occludes the voltage-dependent Ca2+ channel modulation produced by noradrenaline (NA). Conversely, over-expression of Galpha produces minimal effects on basal Ca2+ channel behaviour but attenuates NA-mediated inhibition in a manner consistent with the buffering of Gbetagamma. These observations indicate that it is Gbetagamma, and Galpha, that mediates voltage-dependent inhibition of N-type Ca2+ channels. The identification of Gbetagamma as the mediator of this pathway has broad implications as G-protein-coupled receptors, many of which are implicated in disease or are targets of therapeutic agents, couple to N-type Ca2+ channels and may modulate synaptic transmission by this mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / chemistry
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Cattle
  • Culture Techniques
  • DNA, Complementary
  • Electrochemistry
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Guanylyl Imidodiphosphate / pharmacology
  • Neurons / metabolism*
  • Norepinephrine / pharmacology
  • Rats
  • Sympathetic Nervous System / cytology
  • Sympathetic Nervous System / metabolism


  • Calcium Channels
  • DNA, Complementary
  • Guanylyl Imidodiphosphate
  • GTP-Binding Proteins
  • Norepinephrine