Phosphoinositide 3-kinase isoforms selectively couple receptors to vascular L-type Ca2+ channels

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 brine, evidences that vascular L-type Ca2+ channels can be modulated by both tyrosine kinase-regulated class Ia and G protein-regulated class Ib PUKs. Purified recombinant PI3Ks increased the peak Ca2+ channel current density when applied intracellularly. Furthermore, PI3K alpha-, beta-, and delta -mediated stimulations of Ca2+ channel currents were increased by preactivation by a phosphotyrosyl peptide, whereas PI3K gamma- and beta -mediated effects were increased by G beta gamma. In freshly isolated and cultured vascular myocytes, angiotensin II and G beta gamma 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 alpha and PI3K gamma. Interestingly, when endogenous PI3K beta expression arose in cultured myocytes, both PDGF and phosphotyrosyl peptide stimulated Ca2+ channels through PI3K beta, as revealed by the inhibitory effect of an anti-PI3K beta antibody. These results, suggest that endogenous PI3K beta but not PI3K alpha 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.