G-protein activation mediates prepulse facilitation of Ca2+ channel currents in bovine chromaffin cells

J Membr Biol. 1994 May;140(1):47-56. doi: 10.1007/BF00234485.


The effects of G-protein activation were investigated on tonic, large depolarization-induced Ca2+ channel facilitation in cultured bovine adrenal chromaffin cells. Under whole-cell voltage clamp, activation of G proteins by intracellular dialysis with 200 microM GTP-gamma S did not significantly affect prepulse facilitation or whole-cell Ba2+ current (IBa) density. In contrast, inactivation of G proteins by intracellular GDP-beta S or pertussis toxin (PTX) pretreatment completely abolished or markedly attenuated facilitation of IBa, respectively. GDP-beta S dialysis resulted in nearly a threefold increase in peak IBa density, whereas PTX pretreatment resulted in a 50% increase. Our results indicate that under control recording conditions (200 microM intracellular GTP), G proteins are tonically activated and suppress high-voltage-activated (HVA) Ca2+ channels in a voltage-dependent and voltage-independent manner. Local superfusion of chromaffin cells with normal bath solution produced a rapid and reversible increase (approximately 50%) in IBa amplitudes that also abolished prepulse facilitation. Together, these results demonstrate that tonic facilitation of HVA Ca2+ channels in bovine chromaffin cells involves the voltage-dependent relief of a G-protein-mediated suppression, imposed by chromaffin cell secretory products that feedback and activate G-protein-coupled autoreceptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adrenal Medulla / drug effects
  • Adrenal Medulla / metabolism*
  • Animals
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Catecholamines / metabolism
  • Cattle
  • Cells, Cultured
  • Enkephalins / metabolism
  • GTP-Binding Proteins / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Guanosine Diphosphate / analogs & derivatives
  • Guanosine Diphosphate / pharmacology
  • Membrane Potentials
  • Thionucleotides / pharmacology


  • Calcium Channels
  • Catecholamines
  • Enkephalins
  • Thionucleotides
  • Guanosine Diphosphate
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • guanosine 5'-O-(2-thiodiphosphate)
  • Adenosine Triphosphate
  • GTP-Binding Proteins