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Science 287 (5458): 1647-1651

Copyright © 2000 by the American Association for the Advancement of Science

Requirement of the Inositol Trisphosphate Receptor for Activation of Store-Operated Ca2+ Channels

Hong-Tao Ma, 1* Randen L. Patterson, 1* Damian B. van Rossum, 1 Lutz Birnbaumer, 2 Katsuhiko Mikoshiba, 3 Donald L. Gill 1dagger

The coupling mechanism between endoplasmic reticulum (ER) calcium ion (Ca2+) stores and plasma membrane (PM) store-operated channels (SOCs) is crucial to Ca2+ signaling but has eluded detection. SOCs may be functionally related to the TRP family of receptor-operated channels. Direct comparison of endogenous SOCs with stably expressed TRP3 channels in human embryonic kidney (HEK293) cells revealed that TRP3 channels differ in being store independent. However, condensed cortical F-actin prevented activation of both SOC and TRP3 channels, which suggests that ER-PM interactions underlie coupling of both channels. A cell-permeant inhibitor of inositol trisphosphate receptor (InsP3R) function, 2-aminoethoxydiphenyl borate, prevented both receptor-induced TRP3 activation and store-induced SOC activation. It is concluded that InsP3Rs mediate both SOC and TRP channel opening and that the InsP3R is essential for maintaining coupling between store emptying and physiological activation of SOCs.

1 Department of Biochemistry and Molecular Biology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
2 Department of Anesthesiology, University of California, Los Angeles, CA 90095, USA.
3 Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: dgill{at}

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Effect of flow and stretch on the [Ca2+]i response of principal and intercalated cells in cortical collecting duct.
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Am J Physiol Renal Physiol 285, F998-F1012
   Abstract »    Full Text »    PDF »
NAADP mobilizes Ca2+ from a thapsigargin-sensitive store in the nuclear envelope by activating ryanodine receptors.
J. V. Gerasimenko, Y. Maruyama, K. Yano, N. J. Dolman, A. V. Tepikin, O. H. Petersen, and O. V. Gerasimenko (2003)
J. Cell Biol. 163, 271-282
   Abstract »    Full Text »    PDF »
Store-operated Cation Entry Mediated by CD20 in Membrane Rafts.
H. Li, L. M. Ayer, J. Lytton, and J. P. Deans (2003)
J. Biol. Chem. 278, 42427-42434
   Abstract »    Full Text »    PDF »
RhoA Interaction with Inositol 1,4,5-Trisphosphate Receptor and Transient Receptor Potential Channel-1 Regulates Ca2+ Entry: ROLE IN SIGNALING INCREASED ENDOTHELIAL PERMEABILITY.
D. Mehta, G. U. Ahmmed, B. C. Paria, M. Holinstat, T. Voyno-Yasenetskaya, C. Tiruppathi, R. D. Minshall, and A. B. Malik (2003)
J. Biol. Chem. 278, 33492-33500
   Abstract »    Full Text »    PDF »
C. C. Scott, W. Furuya, W. S. Trimble, and S. Grinstein (2003)
J. Biol. Chem. 278, 30534-30539
   Abstract »    Full Text »    PDF »
Regulation of Canonical Transient Receptor Potential (TRPC) Channel Function by Diacylglycerol and Protein Kinase C.
K. Venkatachalam, F. Zheng, and D. L. Gill (2003)
J. Biol. Chem. 278, 29031-29040
   Abstract »    Full Text »    PDF »
Capacitative Cation Entry in Human Myometrial Cells and Augmentation by hTrpC3 Overexpression.
S. G. Shlykov, M. Yang, J. L. Alcorn, and B. M. Sanborn (2003)
Biol Reprod 69, 647-655
   Abstract »    Full Text »    PDF »
TRPC3 Mediates T-cell Receptor-dependent Calcium Entry in Human T-lymphocytes.
S. Philipp, B. Strauss, D. Hirnet, U. Wissenbach, L. Mery, V. Flockerzi, and M. Hoth (2003)
J. Biol. Chem. 278, 26629-26638
   Abstract »    Full Text »    PDF »
Expression Level of the Canonical Transient Receptor Potential 3 (TRPC3) Channel Determines Its Mechanism of Activation.
G. Vazquez, B. J. Wedel, M. Trebak, G. St. John Bird, and J. W. Putney Jr. (2003)
J. Biol. Chem. 278, 21649-21654
   Abstract »    Full Text »    PDF »
Transient Receptor Potential Channel Activation Causes a Novel Form of [Ca 2+]i Oscillations and Is Not Involved in Capacitative Ca 2+ Entry in Glial Cells.
M. Grimaldi, M. Maratos, and A. Verma (2003)
J. Neurosci. 23, 4737-4745
   Abstract »    Full Text »    PDF »
2-Aminoethoxydiphenyl Borane Activates a Novel Calcium-Permeable Cation Channel.
F.-J. Braun, O. Aziz, and J. W. Putney Jr. (2003)
Mol. Pharmacol. 63, 1304-1311
   Abstract »    Full Text »    PDF »
The Hepatitis C Virus Core Protein Modulates T Cell Responses by Inducing Spontaneous and Altering T-cell Receptor-triggered Ca2+ Oscillations.
A. Bergqvist, S. Sundstrom, L. Y. Dimberg, E. Gylfe, and M. G. Masucci (2003)
J. Biol. Chem. 278, 18877-18883
   Abstract »    Full Text »    PDF »
The {alpha}-Latrotoxin Mutant LTXN4C Enhances Spontaneous and Evoked Transmitter Release in CA3 Pyramidal Neurons.
M. Capogna, K. E. Volynski, N. J. Emptage, and Y. A. Ushkaryov (2003)
J. Neurosci. 23, 4044-4053
   Abstract »    Full Text »    PDF »

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