Phosphoinositide 3-Kinase Isoforms Selectively Couple Receptors to Vascular L-Type Ca 2+ Channels
- 12 October 2001
- journal article
- other
- Published by Wolters Kluwer Health in Circulation Research
- Vol. 89 (8) , 692-699
- https://doi.org/10.1161/hh2001.097864
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, PI3Kα-, β-, and δ-mediated stimulations of Ca2+ channel currents were increased by preactivation by a phosphotyrosyl peptide, whereas PI3Kγ- and β-mediated effects were increased by Gβγ. In freshly isolated and cultured vascular myocytes, angiotensin II and Gβγ 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 PI3Kα and PI3Kγ. Interestingly, when endogenous PI3Kβ expression arose in cultured myocytes, both PDGF and phosphotyrosyl peptide stimulated Ca2+ channels through PI3Kβ, as revealed by the inhibitory effect of an anti-PI3Kβ antibody. These results suggest that endogenous PI3Kβ but not PI3Kα 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.Keywords
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