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(Circulation Research. 2001;89:692.)
© 2001 American Heart Association, Inc.

Cellular Biology

Phosphoinositide 3-Kinase Isoforms Selectively Couple Receptors to Vascular L-Type Ca²⁺ Channels

Nathalie Macrez, Chantal Mironneau, Valérie Carricaburu, Jean-François Quignard, Aleksei Babich, Cornelia Czupalla, Bernd Nürnberg, Jean Mironneau

From Laboratoire de Signalisation et Interactions Cellulaires (N.M., C.M., V.C., J.-F.Q., J.M.), Université de Bordeaux II, France, and Abteilung Pharmakologie und Toxikologie (A.B., C.C., B.N.), Universität Ulm, Germany.

Correspondence to N. Macrez, Laboratoire de Signalisation et Interactions Cellulaires, CNRS UMR 5017, Université de Bordeaux II, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. E-mail nathalie.macrez{at}umr5017.u-bordeaux2.fr

Abstract—— Heterodimeric class I phosphoinositide 3-kinase (PI3K) has been shown to be involved in the stimulation of voltage-gated Ca²⁺ channels by various mediators. In this study, we bring evidences that vascular L-type Ca²⁺ channels can be modulated by both tyrosine kinase–regulated class Ia and G protein–regulated class Ib PI3Ks. Purified recombinant PI3Ks increased the peak Ca²⁺ channel current density when applied intracellularly. Furthermore, PI3K-, ß-, and -mediated stimulations of Ca²⁺ channel currents were increased by preactivation by a phosphotyrosyl peptide, whereas PI3K- and ß-mediated effects were increased by Gß. In freshly isolated and cultured vascular myocytes, angiotensin II and Gß stimulated L-type Ca²⁺ channel current. In contrast, platelet-derived growth factor (PDGF)-BB and the phosphotyrosyl peptide did not stimulate Ca²⁺ channel current in freshly isolated cells despite the presence of endogenous PDGF receptors and PI3K and PI3K. Interestingly, when endogenous PI3Kß expression arose in cultured myocytes, both PDGF and phosphotyrosyl peptide stimulated Ca²⁺ channels through PI3Kß, as revealed by the inhibitory effect of an anti-PI3Kß antibody. These results suggest that endogenous PI3Kß but not PI3K is specifically involved in PDGF receptor–induced stimulation of Ca²⁺ channels and that different isoforms of PI3K regulate physiological increases of Ca²⁺ influx in vascular myocytes stimulated by vasoconstrictor or growth factor.

Key Words: phosphoinositide 3-kinase isoforms • L-type Ca²⁺ channel • smooth muscle • platelet-derived growth factor

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