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J. Biol. Chem. 275 (7): 4561-4564

© 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

J Biol Chem, Vol. 275, Issue 7, 4561-4564, February 18, 2000

Plasma Membrane Calcium Channels in Human Carcinoma A431 Cells Are Functionally Coupled to Inositol 1,4,5-Trisphosphate Receptor-Phosphatidylinositol 4,5-Bisphosphate Complexes*

Elena KaznacheyevaDagger , Alexander ZubovDagger , Anton NikolaevDagger , Vadim AlexeenkoDagger , Ilya Bezprozvanny§, and Galina N. MozhayevaDagger

From the Dagger  Institute of Cytology RAS, 4 Tikhoretsky Ave., St. Petersburg 194064, Russia and the § Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75235

In most nonexcitable cells, calcium (Ca2+) release from inositol 1,4,5-trisphosphate (InsP3)-sensitive intracellular Ca2+ stores is coupled to Ca2+ influx (calcium release-activated channels (ICRAC)) pathway. Despite intense investigation, the molecular identity of ICRAC and the mechanism of its activation remain poorly understood. InsP3-dependent miniature calcium channels (Imin) display functional properties characteristic for ICRAC. Here we used patch clamp recordings of Imin channels in human carcinoma A431 cells to demonstrate that Imin activity was greatly enchanced in the presence of anti-phosphatidylinositol 4,5-bisphosphate antibody (PIP2Ab) and diminished in the presence of PIP2. Anti-PIP2 antibody induced a greater than 6-fold increase in Imin sensitivity for InsP3 activation and an almost 4-fold change in Imin maximal open probability. The addition of exogenous PIP2 vesicles to the cytosolic surface of inside-out patches inhibited Imin activity. These results lead us to propose an existence of a Ca2+ influx pathway in nonexcitable cells activated via direct conformational coupling with a selected population of InsP3 receptors, located just underneath the plasma membrane and coupled to PIP2. The described pathway provides for a highly compartmentalized Ca2+ influx and intracellular Ca2+ store refilling mechanism.

* This work was supported by a grant from the Russian Basic Research Foundation (to G. N. M) and by National Institutes of Health Grant NS38082 (to I. B.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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