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J. Biol. Chem. 275 (13): 9114-9119

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

J Biol Chem, Vol. 275, Issue 13, 9114-9119, March 31, 2000

IARC, a Novel Arachidonate-regulated, Noncapacitative Ca2+ Entry Channel*

Olivier Mignen and Trevor J. ShuttleworthDagger

From the Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642

Along with the inositol trisphosphate-induced release of stored Ca2+, a receptor-enhanced entry of Ca2+ is a critical component of intracellular Ca2+ signals generated by agonists acting at receptors coupled to the activation of phospholipase C. Although the simple emptying of the intracellular Ca2+ stores is known to be capable of activating Ca2+ entry via the so-called "capacitative" mechanism, recent evidence suggests that Ca2+ entry at physiological agonist concentrations, where oscillatory Ca2+ signals are typically observed, does not conform to such a model. Instead, a noncapacitative Ca2+ entry pathway regulated by arachidonic acid appears to be responsible for Ca2+ entry under these conditions. Using whole-cell patch clamp techniques we demonstrate that low concentrations of arachidonic acid activate a Ca2+-selective current that is superficially similar to the store-operated current ICRAC, but which also demonstrates certain distinct features. We have named this novel current IARC (for arachidonate-regulated calcium current). Importantly, IARC can be readily activated in cells whose Ca2+ stores have been maximally depleted. IARC represents a novel Ca2+ entry pathway that is entirely separate from those activated by store depletion and is specifically activated at physiological levels of stimulation.

* This work was supported by National Institute of General Medical Sciences Grant GM 40457.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.

Dagger To whom correspondence should be addressed: Dept. of Pharmacology and Physiology, Box 711, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14642. Tel.: 716-275-2076; Fax: 716-273-2652; E-mail:

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

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