Regulation of Vascular L-type Ca 2+ Channels by Phosphatidylinositol 3,4,5-Trisphosphate
Circulation Research. 2004-08-06; 95(3): 300-307
DOI: 10.1161/01.RES.0000138017.76125.8b
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1. Circ Res. 2004 Aug 6;95(3):300-7. Epub 2004 Jul 8.
Regulation of vascular L-type Ca2+ channels by phosphatidylinositol
3,4,5-trisphosphate.
Le Blanc C(1), Mironneau C, Barbot C, Henaff M, Bondeva T, Wetzker R, Macrez N.
Author information:
(1)Laboratoire de Signalisation et Interactions Cellulaires, Université de
Bordeaux II, Bordeaux, France.
Modulation of voltage-gated L-type Ca2+ channels by phosphoinositide 3-kinase
(PI3K) regulates Ca2+ entry and plays a crucial role in vascular
excitation-contraction coupling. Angiotensin II (Ang II) activates Ca2+ entry by
stimulating L-type Ca2+ channels through Gbeta-sensitive PI3K in portal vein
myocytes. Moreover, PI3K and Ca2+ entry activation have been reported to be
necessary for receptor tyrosine kinase-coupled and G protein-coupled
receptor-induced DNA synthesis in vascular cells. We have previously shown that
tyrosine kinase-regulated class Ia and G protein-regulated class Ib PI3Ks are
able to modulate vascular L-type Ca2+ channels. PI3Ks display 2 enzymatic
activities: a lipid-kinase activity leading to the formation of
phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3 or PIP3] and a
serine-kinase activity. Here we show that exogenous PIP3 applied into the cell
through the patch pipette is able to reproduce the Ca2+ channel-stimulating
effect of Ang II and PI3Ks. Moreover, the Ang II-induced PI3K-mediated
stimulation of Ca2+ channel and the resulting increase in cytosolic Ca2+
concentration are blocked by the anti-PIP3 antibody. Mutants of PI3K transfected
into vascular myocytes also revealed the essential role of the lipid-kinase
activity of PI3K in Ang II-induced Ca2+ responses. These results suggest that
PIP3 is necessary and sufficient to activate a Ca2+ influx in vascular myocytes
stimulated by Ang II.
DOI: 10.1161/01.RES.0000138017.76125.8b
PMID: 15242973 [Indexed for MEDLINE]