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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
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