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

• Published in: The Journal of physiology 1998-01, Vol.506 (2), p.319-329
• Main Authors: Delmas, Patrick, Brown, David A., Dayrell, Mariza, Abogadie, Fe C., Caulfield, Malcolm P., Buckley, Noel J.
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 0022-3751; 1469-7793
• 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 βγ 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 β‐adrenergic receptor kinase 1 (βARK1), which contains the consensus motif (QXXER) for binding Gβγ, 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. βARK1 peptide reduced GTP‐γ‐S‐induced voltage‐dependent and PTX‐sensitive inhibition of ICa but not GTP‐γ‐S‐mediated voltage‐independent inhibition. 3 Overexpression of Gβ1γ2, 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 βARK1 with β1 and γ2 subunits prevented the effects of Gβγ dimers on basal Ca2+ channel behaviour in a manner consistent with the sequestering of Gβγ. 5 The expression of the C‐terminus of βARK1 slowed down reinhibition kinetics of ICa following conditioning depolarizations and induced long‐lasting facilitation by cumulatively sequestering βγ subunits. 6 Our findings identify endogenous Gβγ 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 Gβγ‐Ca2+ channel interaction.