This Article Full Text Full Text (PDF) All Versions of this Article: 95/3/300    most recent 01.RES.0000138017.76125.8bv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Le Blanc, C. Articles by Macrez, N. Search for Related Content PubMed PubMed Citation Articles by Le Blanc, C. Articles by Macrez, N. Related Collections Calcium cycling/excitation-contraction coupling Cell signalling/signal transduction Ion channels/membrane transport

(Circulation Research. 2004;95:300.)
© 2004 American Heart Association, Inc.

Cellular Biology

Regulation of Vascular L-type Ca²⁺ Channels by Phosphatidylinositol 3,4,5-Trisphosphate

Catherine Le Blanc, Chantal Mironneau, Caroline Barbot, Morgana Henaff, Tzvetanka Bondeva, Reinhard Wetzker, Nathalie Macrez

From the Laboratoire de Signalisation et Interactions Cellulaires (C.L.B., C.M., C.B., M.H., N.M.), Université de Bordeaux II, Bordeaux, France; and the Research Unit "Molecular Cell Biology" (T.B., R.W.), University of Jena, Jena, Germany.

Correspondence to Nathalie 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

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 Gß-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.

Key Words: L-type Ca²⁺ channel • PI3K • PIP3 • angiotensin II • smooth muscle

This article has been cited by other articles:

				C. O'Neill Phosphatidylinositol 3-kinase signaling in mammalian preimplantation embryo development Reproduction, August 1, 2008; 136(2): 147 - 156. [Abstract] [Full Text] [PDF]

				Y. Li, V. Chandrakanthan, M. L Day, and C. O'Neill Direct Evidence for the Action of Phosphatidylinositol (3,4,5)-Trisphosphate-Mediated Signal Transduction in the 2-Cell Mouse Embryo Biol Reprod, November 1, 2007; 77(5): 813 - 821. [Abstract] [Full Text] [PDF]

				E. Hirsch, C. Costa, and E. Ciraolo Phosphoinositide 3-kinases as a common platform for multi-hormone signaling J. Endocrinol., August 1, 2007; 194(2): 243 - 256. [Abstract] [Full Text] [PDF]

				C.-T. Tsai, D. L. Wang, W.-P. Chen, J.-J. Hwang, C.-S. Hsieh, K.-L. Hsu, C.-D. Tseng, L.-P. Lai, Y.-Z. Tseng, F.-T. Chiang, et al. Angiotensin II Increases Expression of {alpha}1C Subunit of L-Type Calcium Channel Through a Reactive Oxygen Species and cAMP Response Element-Binding Protein-Dependent Pathway in HL-1 Myocytes Circ. Res., May 25, 2007; 100(10): 1476 - 1485. [Abstract] [Full Text] [PDF]

				D. Chansel, M. Ciroldi, S. Vandermeersch, L. F Jackson, A.-M. Gomez, D. Henrion, D. C. Lee, T. M. Coffman, S. Richard, J.-C. Dussaule, et al. Heparin binding EGF is necessary for vasospastic response to endothelin FASEB J, September 1, 2006; 20(11): 1936 - 1938. [Abstract] [Full Text] [PDF]

				T. Kobayashi, Y. Hayashi, K. Taguchi, T. Matsumoto, and K. Kamata ANG II enhances contractile responses via PI3-kinase p110{delta} pathway in aortas from diabetic rats with systemic hyperinsulinemia Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H846 - H853. [Abstract] [Full Text] [PDF]

				H. Sun, B.-G. Kerfant, D. Zhao, M. G. Trivieri, G. Y. Oudit, J. M. Penninger, and P. H. Backx Insulin-Like Growth Factor-1 and PTEN Deletion Enhance Cardiac L-Type Ca2+ Currents via Increased PI3K{alpha}/PKB Signaling Circ. Res., June 9, 2006; 98(11): 1390 - 1397. [Abstract] [Full Text] [PDF]

				J. M. Eltit, A. A. Garcia, J. Hidalgo, J. L. Liberona, M. Chiong, S. Lavandero, E. Maldonado, and E. Jaimovich Membrane Electrical Activity Elicits Inositol 1,4,5-Trisphosphate-dependent Slow Ca2+ Signals through a Gbeta{gamma}/Phosphatidylinositol 3-Kinase {gamma} Pathway in Skeletal Myotubes J. Biol. Chem., April 28, 2006; 281(17): 12143 - 12154. [Abstract] [Full Text] [PDF]

				Z. Lu, Y.-P. Jiang, L. M. Ballou, I. S. Cohen, and R. Z. Lin G{alpha}q Inhibits Cardiac L-type Ca2+ Channels through Phosphatidylinositol 3-Kinase J. Biol. Chem., December 2, 2005; 280(48): 40347 - 40354. [Abstract] [Full Text] [PDF]

				S. B. Milne, P. T. Ivanova, D. DeCamp, R. C. Hsueh, and H. A. Brown A targeted mass spectrometric analysis of phosphatidylinositol phosphate species J. Lipid Res., August 1, 2005; 46(8): 1796 - 1802. [Abstract] [Full Text] [PDF]

				N. Fritz, N. Macrez, J. Mironneau, L. H. Jeyakumar, S. Fleischer, and J.-L. Morel Ryanodine receptor subtype 2 encodes Ca2+ oscillations activated by acetylcholine via the M2 muscarinic receptor/cADP-ribose signalling pathway in duodenum myocytes J. Cell Sci., May 15, 2005; 118(10): 2261 - 2270. [Abstract] [Full Text] [PDF]

				A. Welling, F. Hofmann, and J. W. Wegener Inhibition of L-Type Cav1.2 Ca2+ Channels by 2,(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) and 2-[1-(3-Dimethyl-aminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl) Maleimide (Go6983) Mol. Pharmacol., February 1, 2005; 67(2): 541 - 544. [Abstract] [Full Text] [PDF]