Heterodimeric class I phosphoinositide 3-kinase (PI3K) has been shown to be
involved in the stimulation of voltage-gated Ca2+ channels by various medi
ators. In this study, we brine, evidences that vascular L-type Ca2+ channel
s 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 a
lpha-, beta-, and delta -mediated stimulations of Ca2+ channel currents wer
e increased by preactivation by a phosphotyrosyl peptide, whereas PI3K gamm
a- and beta -mediated effects were increased by G beta gamma. In freshly is
olated and cultured vascular myocytes, angiotensin II and G beta gamma stim
ulated L-type Ca2+ channel current. In contrast, platelet-derived growth fa
ctor (PDGF)-BB and the phosphotyrosyl peptide did not stimulate Ca2+ channe
l current in freshly isolated cells despite the presence of endogenous PDGF
receptors and PI3K alpha and PI3K gamma. Interestingly, when endogenous PI
3K beta expression arose in cultured myocytes, both PDGF and phosphotyrosyl
peptide stimulated Ca2+ channels through PI3K beta, as revealed by the inh
ibitory effect of an anti-PI3K beta antibody. These results, suggest that e
ndogenous PI3K beta but not PI3K alpha is specifically involved in PDGF rec
eptor-induced stimulation of Ca2+ channels and that different isoforms of P
I3K regulate physiological increases of Ca2+ influx in vascular myocytes st
imulated by vasoconstrictor or growth factor.