Facilitation of rabbit alpha1B calcium channels: involvement of endogenous Gbetagamma subunits

The Journal of Physiology
Gary J StephensA C Dolphin

Abstract

1. The alpha1B (N-type) calcium channel shows strong G protein modulation in the presence of G protein activators or Gbetagamma subunits. Using transient expression in COS-7 cells of alpha1B together with the accessory subunits alpha2-delta and beta2a, we have examined the role of endogenous Gbetagamma subunits in the tonic modulation of alpha1B, and compared this with modulation by exogenously expressed Gbetagamma subunits. 2. Prepulse facilitation of control alpha1B/alpha2-delta/beta2a currents was always observed. This suggests the existence of tonic modulation of alpha1B subunits. To determine whether endogenous Gbetagamma is involved in the facilitation observed in control conditions, the betaARK1 Gbetagamma-binding domain (amino acids 495-689) was overexpressed, in order to bind free Gbetagamma subunits. The extent of control prepulse-induced facilitation was significantly reduced, both in terms of current amplitude and the rate of current activation. In agreement with this, GDPbetaS also reduced the control facilitation. 3. Co-expression of the Gbeta1gamma2 subunit, together with the alpha1B/alpha2-delta/beta2a calcium channel combination, resulted in a marked degree of depolarizing prepulse-reversible inhibition of the ...Continue Reading

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Citations

Jul 25, 2008·Pflügers Archiv : European journal of physiology·Andriy V DresviannikovAnnette C Dolphin
Jun 5, 2008·The Journal of Pharmacology and Experimental Therapeutics·Christopher MorreyRoberto Levi
Jun 17, 1998·The Journal of Physiology·G J StephensA C Dolphin
Aug 18, 2004·Nature Neuroscience·Patricia ViardAnnette C Dolphin
Nov 21, 2007·Acta Physiologica·A P FoxZ Xie
Apr 28, 2011·The Journal of Physiology·Giovanna BucciGary J Stephens
Dec 6, 2003·Pharmacological Reviews·Annette C Dolphin
Jan 1, 2015·Molecular Pharmacology·Juliane Proft, Norbert Weiss

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