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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.

Type

Journal article

Journal

J Physiol

Publication Date

15/01/1998

Volume

506 ( Pt 2)

Pages

319 - 329

Keywords

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