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This Article Full Text Full Text (PDF) All Versions of this Article: 567/3/787    most recent jphysiol.2005.090209v1 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, University of Rochester Medical Center, Rochester, NY 14642, USA
² CNRS UMR 8078, Université Paris Sud, Hôpital Marie Lannelongue, 92350 Le Plessis-Robinson, France

In many non-excitable cells, the predominant mode of agonist-activated Ca²⁺ entry switches from the arachidonic acid-regulated Ca²⁺ (ARC) channels at low agonist concentrations, to store-operated channels at high concentrations. Underlying this process is the inhibition of the ARC channels by a calcineurin-mediated dephosphorylation, which inhibits the ability of arachidonic acid to activate the channels. Following such a dephosphorylation, we found that restoration of the sensitivity of the ARC channels to arachidonic acid, as well as to low concentrations of carbachol, was specifically dependent on protein kinase A (PKA) activity. Inhibition of protein kinase C, protein kinase G or calmodulin-activated kinase had no effect. This action of PKA was unaffected by prolonged intracellular dialysis, whilst disruption of the binding of PKA to A-kinase anchoring proteins (AKAPs) inhibited currents through ARC channels, and blocked the PKA-dependent effects. AKAP79, a protein which scaffolds both PKA and calcineurin, was shown to be present in the cells. These data illustrate the significance of PKA-dependent phosphorylation and calcineurin-dependent dephosphorylation in the overall regulation of ARC channel activity, and indicate the key role of an AKAP, possibly AKAP79, in the spatial organization these processes.

(Received 9 May 2005; accepted after revision 24 June 2005; first published online 30 June 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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