Gbetagamma dimers stimulate vascular L-type Ca2+ channels via phosphoinositide 3-kinase.

Patricia Viard, Torsten Exner, Udo Maier, Jean Mironneau, Bernd Nürnberg, Nathalie Macrez
FASEB j.. 1999-04-01; 13(6): 685-694
DOI: 10.1096/fasebj.13.6.685

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1. FASEB J. 1999 Apr;13(6):685-94.

Gbetagamma dimers stimulate vascular L-type Ca2+ channels via phosphoinositide

Viard P(1), Exner T, Maier U, Mironneau J, Nürnberg B, Macrez N.

Author information:
(1)Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, CNRS ESA
5017, Université de Bordeaux II, 33076 Bordeaux, France.

We have previously reported that, in venous myocytes, Gbetagamma scavengers
inhibit angiotensin AT1A receptor-induced stimulation of L-type Ca2+ channels
(1). Here, we demonstrate that intracellular infusion of purified Gbetagamma
complexes stimulates the L-type Ca2+ channel current in a concentration-dependent
manner. Additional intracellular dialysis of GDP-bound inactive Galphao or of a
peptide corresponding to the Gbetagamma binding region of the beta-adrenergic
receptor kinase completely inhibited the Gbetagamma-induced stimulation of Ca2+
channel currents. The gating properties of the channel were not affected by
intracellular application of Gbetagamma, suggesting that Gbetagamma increased the
whole-cell calcium conductance. In addition, both the angiotensin AT1A receptor-
and the Gbetagamma-induced stimulation of L-type Ca2+ channels were blocked by
pretreatment of the cells with wortmannin, at nanomolar concentrations.
Correspondingly, intracellular infusion of an enzymatically active purified
recombinant Gbetagamma-sensitive phosphoinositide 3-kinase, PI3Kgamma, mimicked
Gbetagamma-induced stimulation of Ca2+ channels. Both Gbetagamma- and
PI3Kgamma-induced stimulations of Ca2+ channel currents were reduced by protein
kinase C inhibitors suggesting that the Gbetagamma/PI3Kgamma-activated
transduction pathway involves a protein kinase C. These results indicate for the
first time that Gbetagamma dimers stimulate the vascular L-type Ca2+ channels
through a Gbetagamma-sensitive PI3K.

DOI: 10.1096/fasebj.13.6.685
PMID: 10094929 [Indexed for MEDLINE]

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