HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 564/3/791    most recent jphysiol.2005.085704v2 jphysiol.2005.085704v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mignen, O. Articles by Shuttleworth, T. J. Search for Related Content PubMed PubMed Citation Articles by Mignen, O. Articles by Shuttleworth, T. J.

¹ Department of Pharmacology and Physiology
² and the Center for Oral Biology, University of Rochester Medical Center, Rochester, NY, USA

ARC channels (arachidonate-regulated Ca²⁺-selective channels) are a novel type of highly Ca²⁺-selective channel that are specifically activated by low concentrations of agonist-induced arachidonic acid. This activation occurs in the absence of any depletion of internal Ca²⁺ stores (i.e. they are ‘non-capacitative’). Previous studies in HEK293 cells have shown that these channels provide the predominant pathway for the entry of Ca²⁺ seen at low agonist concentrations where oscillatory [Ca²⁺]_i signals are typically produced. In contrast, activation of the more widely studied store-operated Ca²⁺ channels (e.g. CRAC channels) is only seen at higher agonist concentrations where sustained ‘plateau-type’[Ca²⁺]_i responses are observed. We have now demonstrated the presence of ARC channels in both parotid and pancreatic acinar cells and shown that, again, they are specifically activated by the low concentrations of appropriate agonists (carbachol in the parotid, and both carbachol and cholecystokinin in the pancreas) that are associated with oscillatory [Ca²⁺]_i signals in these cells. Uncoupling the receptor-mediated activation of cytosolic phospholipase A₂ (cPLA₂) with isotetrandrine reduces the activation of the ARC channels by carbachol and, correspondingly, markedly inhibits the [Ca²⁺]_i signals induced by low carbachol concentrations, whilst those signals seen at high agonist concentrations are essentially unaffected. Interestingly, in the pancreatic acinar cells, activation by cholecystokinin induces a current through the ARC channels that is only approximately 60% of that seen with carbachol. This is consistent with previous reports indicating that carbachol-induced [Ca²⁺]_i signals in these cells are much more dependent on Ca²⁺ entry than are the cholecystokinin-induced responses.

(Received 23 February 2005; accepted after revision 7 March 2005; first published online 10 March 2005)
Corresponding author T. J. Shuttleworth: Department of Pharmacology and Physiology, Box 711, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA. Email: trevor_shuttleworth{at}urmc.rochester.edu

This article has been cited by other articles:

				O. Mignen, J. L. Thompson, and T. J. Shuttleworth Both Orai1 and Orai3 are essential components of the arachidonate-regulated Ca2+-selective (ARC) channels J. Physiol., January 1, 2008; 586(1): 185 - 195. [Abstract] [Full Text] [PDF]

				J. W. Putney Jr New molecular players in capacitative Ca2+ entry J. Cell Sci., June 15, 2007; 120(12): 1959 - 1965. [Abstract] [Full Text] [PDF]

				O. Mignen, J. L. Thompson, and T. J. Shuttleworth STIM1 regulates Ca2+ entry via arachidonate-regulated Ca2+-selective (ARC) channels without store depletion or translocation to the plasma membrane J. Physiol., March 15, 2007; 579(3): 703 - 715. [Abstract] [Full Text] [PDF]

				B. Wedel, R. R. Boyles, J. W. Putney Jr, and G. S. Bird Role of the store-operated calcium entry proteins Stim1 and Orai1 in muscarinic cholinergic receptor-stimulated calcium oscillations in human embryonic kidney cells J. Physiol., March 15, 2007; 579(3): 679 - 689. [Abstract] [Full Text] [PDF]

				R. C. Hardie TRP channels and lipids: from Drosophila to mammalian physiology J. Physiol., January 1, 2007; 578(1): 9 - 24. [Abstract] [Full Text] [PDF]

				J. H. Won and D. I. Yule Measurement of Ca2+ signaling dynamics in exocrine cells with total internal reflection microscopy Am J Physiol Gastrointest Liver Physiol, July 1, 2006; 291(1): G146 - G155. [Abstract] [Full Text] [PDF]

				O. Mignen, C. Brink, A. Enfissi, A. Nadkarni, T. J. Shuttleworth, D. R. Giovannucci, and T. Capiod Carboxyamidotriazole-induced inhibition of mitochondrial calcium import blocks capacitative calcium entry and cell proliferation in HEK-293 cells J. Cell Sci., December 1, 2005; 118(23): 5615 - 5623. [Abstract] [Full Text] [PDF]

				O. Mignen, J. L Thompson, and T. J Shuttleworth Arachidonate-regulated Ca2+-selective (ARC) channel activity is modulated by phosphorylation and involves an A-kinase anchoring protein J. Physiol., September 15, 2005; 567(3): 787 - 798. [Abstract] [Full Text] [PDF]