On the role of endogenous G-protein beta gamma subunits in N-type Ca2+ current inhibition by neurotransmitters in rat sympathetic neurones

J Physiol. 1998 Jan 15;506 ( Pt 2)(Pt 2):319-29. doi: 10.1111/j.1469-7793.1998.319bw.x.


1. Using whole-cell and perforated-patch recordings, we have examined the part played by endogenous G-protein beta gamma subunits in neurotransmitter-mediated inhibition of N-type Ca2+ channel current (ICa) in dissociated rat superior cervical sympathetic neurones. 2. Expression of the C-terminus domain of beta-adrenergic receptor kinase 1 (beta ARK1), which contains the consensus motif (QXXER) for binding G beta gamma, reduced the fast (pertussis toxin (PTX)-sensitive) and voltage-dependent inhibition of ICa by noradrenaline and somatostatin, but not the slow (PTX-insensitive) and voltage-independent inhibition induced by angiotensin II. beta ARK1 peptide reduced GTP-gamma-S-induced voltage-dependent and PTX-sensitive inhibition of ICa but not GTP-gamma-S-mediated voltage-independent inhibition. 3. Overexpression of G beta 1 gamma 2, which mimicked the voltage-dependent inhibition by reducing ICa density and enhancing basal facilitation, occluded the voltage-dependent noradrenaline- and somatostatin-mediated inhibitions but not the inhibition mediated by angiotensin II. 4. Co-expression of the C-terminus of beta ARK1 with beta 1 and gamma 2 subunits prevented the effects of G beta gamma dimers on basal Ca2+ channel behaviour in a manner consistent with the sequestering of G beta gamma. 5. The expression of the C-terminus of beta ARK1 slowed down reinhibition kinetics of ICa following conditioning depolarizations and induced long-lasting facilitation by cumulatively sequestering beta gamma subunits. 6. Our findings identify endogenous G beta gamma as the mediator of the voltage-dependent, PTX-sensitive inhibition of ICa induced by both noradrenaline and somatostatin but not the voltage-independent. PTX-insensitive inhibition by angiotensin II. They also support the view that voltage-dependent inhibition results from a direct G beta gamma-Ca2+ channel interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology
  • Animals
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / physiology
  • Electrophysiology
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / physiology*
  • Gene Expression / genetics
  • Gene Expression / physiology
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Humans
  • Ion Channel Gating
  • Kinetics
  • Neurons / chemistry
  • Neurons / drug effects
  • Neurons / physiology
  • Neurotransmitter Agents / physiology*
  • Norepinephrine / antagonists & inhibitors
  • Norepinephrine / pharmacology
  • Pertussis Toxin
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha / physiology
  • Receptors, Somatostatin / physiology
  • Recombinant Proteins / genetics
  • Somatostatin / antagonists & inhibitors
  • Somatostatin / pharmacology
  • Superior Cervical Ganglion / chemistry
  • Superior Cervical Ganglion / cytology*
  • Time Factors
  • Virulence Factors, Bordetella / pharmacology
  • beta-Adrenergic Receptor Kinases


  • Calcium Channels
  • Neurotransmitter Agents
  • Receptors, Adrenergic, alpha
  • Receptors, Somatostatin
  • Recombinant Proteins
  • Virulence Factors, Bordetella
  • Angiotensin II
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Somatostatin
  • Pertussis Toxin
  • Cyclic AMP-Dependent Protein Kinases
  • beta-Adrenergic Receptor Kinases
  • GTP-Binding Proteins
  • Norepinephrine