Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

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

ACCELERATED PUBLICATION
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: trevor_shuttleworth@urmc.rochester.edu.

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

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Orai3 - the 'exceptional' Orai?.
T. J. Shuttleworth (2012)
J. Physiol. 590, 241-257
   Abstract »    Full Text »    PDF »
The molecular architecture of the arachidonate-regulated Ca2+-selective ARC channel is a pentameric assembly of Orai1 and Orai3 subunits.
O. Mignen, J. L. Thompson, and T. J. Shuttleworth (2009)
J. Physiol. 587, 4181-4197
   Abstract »    Full Text »    PDF »
The Orai1 Severe Combined Immune Deficiency Mutation and Calcium Release-activated Ca2+ Channel Function in the Heterozygous Condition.
J. L. Thompson, O. Mignen, and T. J. Shuttleworth (2009)
J. Biol. Chem. 284, 6620-6626
   Abstract »    Full Text »    PDF »
Thermal tolerance of contractile function in oxidative skeletal muscle: no protection by antioxidants and reduced tolerance with eicosanoid enzyme inhibition.
S. R. Oliver, V. P. Wright, N. Parinandi, and T. L. Clanton (2008)
Am J Physiol Regulatory Integrative Comp Physiol 295, R1695-R1705
   Abstract »    Full Text »    PDF »
Free fatty acids act as endogenous ionophores, resulting in Na+ and Ca2+ influx and myocyte apoptosis.
K.-M. Fang, A.-S. Lee, M.-J. Su, C.-L. Lin, C.-L. Chien, and M.-L. Wu (2008)
Cardiovasc Res 78, 533-545
   Abstract »    Full Text »    PDF »
Ceramide kinase promotes Ca2+ signaling near IgG-opsonized targets and enhances phagolysosomal fusion in COS-1 cells.
V. Hinkovska-Galcheva, A. Clark, S. VanWay, J.-B. Huang, M. Hiraoka, A. Abe, M. Borofsky, R. G. Kunkel, T. Shanley, J. A. Shayman, et al. (2008)
J. Lipid Res. 49, 531-542
   Abstract »    Full Text »    PDF »
Both Orai1 and Orai3 are essential components of the arachidonate-regulated Ca2+-selective (ARC) channels.
O. Mignen, J. L. Thompson, and T. J. Shuttleworth (2008)
J. Physiol. 586, 185-195
   Abstract »    Full Text »    PDF »
Phospholipases and fatty acid signalling in exocytosis.
F. Darios, E. Connell, and B. Davletov (2007)
J. Physiol. 585, 699-704
   Abstract »    Full Text »    PDF »
STIM1 regulates Ca2+ entry via arachidonate-regulated Ca2+-selective (ARC) channels without store depletion or translocation to the plasma membrane.
O. Mignen, J. L. Thompson, and T. J. Shuttleworth (2007)
J. Physiol. 579, 703-715
   Abstract »    Full Text »    PDF »
Real-time lung microscopy.
W. M. Kuebler, K. Parthasarathi, J. Lindert, and J. Bhattacharya (2007)
J Appl Physiol 102, 1255-1264
   Abstract »    Full Text »    PDF »
TRP channels and lipids: from Drosophila to mammalian physiology.
R. C. Hardie (2007)
J. Physiol. 578, 9-24
   Abstract »    Full Text »    PDF »
Ca2+-independent Phospholipase A2-dependent Gating of TRPM8 by Lysophospholipids.
F. V. Abeele, A. Zholos, G. Bidaux, Y. Shuba, S. Thebault, B. Beck, M. Flourakis, Y. Panchin, R. Skryma, and N. Prevarskaya (2006)
J. Biol. Chem. 281, 40174-40182
   Abstract »    Full Text »    PDF »
Evidence against Calcium as a Mediator of Mitochondrial Dysfunction during Apoptosis Induced by Arachidonic Acid and Other Free Fatty Acids.
R. C. Maia, C. A. Culver, and S. M. Laster (2006)
J. Immunol. 177, 6398-6404
   Abstract »    Full Text »    PDF »
Function of a STIM1 Homologue in C. elegans: Evidence that Store-operated Ca2+ Entry Is Not Essential for Oscillatory Ca2+ Signaling and ER Ca2+ Homeostasis.
X. Yan, J. Xing, C. Lorin-Nebel, A. Y. Estevez, K. Nehrke, T. Lamitina, and K. Strange (2006)
J. Gen. Physiol. 128, 443-459
   Abstract »    Full Text »    PDF »
Cell signaling underlying the pathophysiology of pneumonia.
A. S. Prince, J. P. Mizgerd, J. Wiener-Kronish, and J. Bhattacharya (2006)
Am J Physiol Lung Cell Mol Physiol 291, L297-L300
   Abstract »    Full Text »    PDF »
Carboxyamidotriazole-induced inhibition of mitochondrial calcium import blocks capacitative calcium entry and cell proliferation in HEK-293 cells.
O. Mignen, C. Brink, A. Enfissi, A. Nadkarni, T. J. Shuttleworth, D. R. Giovannucci, and T. Capiod (2005)
J. Cell Sci. 118, 5615-5623
   Abstract »    Full Text »    PDF »
Cl-secretion in ATP-treated renal epithelial C7-MDCK cells is mediated by activation of P2Y1 receptors, phospholipase A2 and protein kinase A.
A. O. Akimova, N. Bourcier, S. Taurin, R. A Bundey, K. Grygorczyk, M. Gekle, P. A Insel, N. O Dulin, and S. N Orlov (2005)
J. Physiol. 568, 789-801
   Abstract »    Full Text »    PDF »
Arachidonate-regulated Ca2+-selective (ARC) channel activity is modulated by phosphorylation and involves an A-kinase anchoring protein.
O. Mignen, J. L Thompson, and T. J Shuttleworth (2005)
J. Physiol. 567, 787-798
   Abstract »    Full Text »    PDF »
Agonist activation of arachidonate-regulated Ca2+-selective (ARC) channels in murine parotid and pancreatic acinar cells.
O. Mignen, J. L. Thompson, D. I. Yule, and T. J. Shuttleworth (2005)
J. Physiol. 564, 791-801
   Abstract »    Full Text »    PDF »
Simultaneous changes of cell volume and cytosolic calcium concentration in macula densa cells caused by alterations of luminal NaCl concentration.
R. Liu and A. E. G Persson (2005)
J. Physiol. 563, 895-901
   Abstract »    Full Text »    PDF »
ARC Channels: A Novel Pathway for Receptor-Activated Calcium Entry.
T. J. Shuttleworth, J. L. Thompson, and O. Mignen (2004)
Physiology 19, 355-361
   Abstract »    Full Text »    PDF »
A New Regulation of Non-capacitative Calcium Entry in Insect Pacemaker Neurosecretory Neurons: INVOLVEMENT OF ARACHIDONIC ACID, NO-GUANYLYL CYCLASE/cGMP, AND cAMP.
D. Wicher, S. Messutat, C. Lavialle, and B. Lapied (2004)
J. Biol. Chem. 279, 50410-50419
   Abstract »    Full Text »    PDF »
Stimulation of Human Spermatozoa with Progesterone Gradients to Simulate Approach to the Oocyte: INDUCTION OF [Ca2+]i OSCILLATIONS AND CYCLICAL TRANSITIONS IN FLAGELLAR BEATING.
C. V. Harper, C. L. R. Barratt, and S. J. Publicover (2004)
J. Biol. Chem. 279, 46315-46325
   Abstract »    Full Text »    PDF »
Toward a Consensus on the Operation of Receptor-Induced Calcium Entry Signals.
D. L. Gill and R. L. Patterson (2004)
Sci. STKE 2004, pe39
   Abstract »    Full Text »    PDF »
Receptor-Activated Calcium Entry Channels--Who Does What, and When?.
T. J. Shuttleworth (2004)
Sci. STKE 2004, pe40
   Abstract »    Full Text »    PDF »
5-HT induces an arachidonic acid-sensitive calcium influx in rat small intrapulmonary artery.
C. Guibert, R. Marthan, and J.-P. Savineau (2004)
Am J Physiol Lung Cell Mol Physiol 286, L1228-L1236
   Abstract »    Full Text »    PDF »
Angiotensin II Stimulates Calcium and Nitric Oxide Release From Macula Densa Cells Through AT1 Receptors.
R. Liu and A. E. G. Persson (2004)
Hypertension 43, 649-653
   Abstract »    Full Text »    PDF »
Control of calcium oscillations by membrane fluxes.
J. Sneyd, K. Tsaneva-Atanasova, D. I. Yule, J. L. Thompson, and T. J. Shuttleworth (2004)
PNAS 101, 1392-1396
   Abstract »    Full Text »    PDF »
Critical role for NHE1 in intracellular pH regulation in pancreatic acinar cells.
D. A. Brown, J. E. Melvin, and D. I. Yule (2003)
Am J Physiol Gastrointest Liver Physiol 285, G804-G812
   Abstract »    Full Text »    PDF »
Calcineurin Directs the Reciprocal Regulation of Calcium Entry Pathways in Nonexcitable Cells.
O. Mignen, J. L. Thompson, and T. J. Shuttleworth (2003)
J. Biol. Chem. 278, 40088-40096
   Abstract »    Full Text »    PDF »
Phospholipase C and phosphatidylinositol 3-kinase signaling are involved in the exogenous arachidonic acid-stimulated respiratory burst in human neutrophils.
J. Liu, Z. Liu, S. Chuai, and X. Shen (2003)
J. Leukoc. Biol. 74, 428-437
   Abstract »    Full Text »    PDF »
Identification of Store-independent and Store-operated Ca2+ Conductances in Caenorhabditis elegans Intestinal Epithelial Cells.
A. Y. Estevez, R. K. Roberts, and K. Strange (2003)
J. Gen. Physiol. 122, 207-223
   Abstract »    Full Text »    PDF »
Interleukin-1{beta} Induces Calcium Transients and Enhances Basal and Store Operated Calcium Entry in Human Myometrial Smooth Muscle.
R. M. Tribe, P. Moriarty, A. Dalrymple, A. A. Hassoni, and L. Poston (2003)
Biol Reprod 68, 1842-1849
   Abstract »    Full Text »    PDF »
Ca2+-independent Phospholipase A2 Is a Novel Determinant of Store-operated Ca2+ Entry.
T. Smani, S. I. Zakharov, E. Leno, P. Csutora, E. S. Trepakova, and V. M. Bolotina (2003)
J. Biol. Chem. 278, 11909-11915
   Abstract »    Full Text »    PDF »
Ca2+ Selectivity and Fatty Acid Specificity of the Noncapacitative, Arachidonate-regulated Ca2+ (ARC) Channels.
O. Mignen, J. L. Thompson, and T. J. Shuttleworth (2003)
J. Biol. Chem. 278, 10174-10181
   Abstract »    Full Text »    PDF »
Arachidonic Acid Plays a Role in Rat Vomeronasal Signal Transduction.
M. Spehr, H. Hatt, and C. H. Wetzel (2002)
J. Neurosci. 22, 8429-8437
   Abstract »    Full Text »    PDF »
The Recombinant Human TRPV6 Channel Functions as Ca2+ Sensor in Human Embryonic Kidney and Rat Basophilic Leukemia Cells.
M. Bodding, U. Wissenbach, and V. Flockerzi (2002)
J. Biol. Chem. 277, 36656-36664
   Abstract »    Full Text »    PDF »
Calcium-Independent Phospholipase A2-Derived Arachidonic Acid Is Essential for Endothelium-Dependent Relaxation by Acetylcholine.
H. C. Seegers, R. W. Gross, and W. A. Boyle (2002)
J. Pharmacol. Exp. Ther. 302, 918-923
   Abstract »    Full Text »    PDF »
Purinergic Receptor Signaling at the Basolateral Membrane of Macula Densa Cells.
R. Liu, P. D. Bell, J. Peti-Peterdi, G. Kovacs, A. Johansson, and A. E. G. Persson (2002)
J. Am. Soc. Nephrol. 13, 1145-1151
   Abstract »    Full Text »    PDF »
The Role of Endogenous Human Trp4 in Regulating Carbachol-induced Calcium Oscillations in HEK-293 Cells.
X. Wu, G. Babnigg, T. Zagranichnaya, and M. L. Villereal (2002)
J. Biol. Chem. 277, 13597-13608
   Abstract »    Full Text »    PDF »
A2 adenosine receptors regulate CFTR through PKA and PLA2.
B. R. Cobb, F. Ruiz, C. M. King, J. Fortenberry, H. Greer, T. Kovacs, E. J. Sorscher, and J. P. Clancy (2002)
Am J Physiol Lung Cell Mol Physiol 282, L12-L25
   Abstract »    Full Text »    PDF »
Role of Ca2+ Stores in Metabotropic L-Glutamate Receptor-Mediated Supralinear Ca2+ Signaling in Rat Hippocampal Neurons.
M. G. Rae, D. J. Martin, G. L. Collingridge, and A. J. Irving (2000)
J. Neurosci. 20, 8628-8636
   Abstract »    Full Text »    PDF »
Signaling Pathways Underlying Muscarinic Receptor-induced [Ca2+]i Oscillations in HEK293 Cells.
D. Luo, L. M. Broad, G. St. J. Bird, and J. W. Putney Jr. (2001)
J. Biol. Chem. 276, 5613-5621
   Abstract »    Full Text »    PDF »
Mutual Antagonism of Calcium Entry by Capacitative and Arachidonic Acid-mediated Calcium Entry Pathways.
D. Luo, L. M. Broad, G. St. J. Bird, and J. W. Putney Jr. (2001)
J. Biol. Chem. 276, 20186-20189
   Abstract »    Full Text »    PDF »
Permeation of Monovalent Cations through the Non-capacitative Arachidonate-regulated Ca2+ Channels in HEK293 Cells. COMPARISON WITH ENDOGENOUS STORE-OPERATED CHANNELS.
O. Mignen and T. J. Shuttleworth (2001)
J. Biol. Chem. 276, 21365-21374
   Abstract »    Full Text »    PDF »
Reciprocal Regulation of Capacitative and Arachidonate-regulated Noncapacitative Ca2+ Entry Pathways.
O. Mignen, J. L. Thompson, and T. J. Shuttleworth (2001)
J. Biol. Chem. 276, 35676-35683
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882