Arachidonate-regulated Ca2+-selective (ARC) channel activity is modulated by phosphorylation and involves an A-kinase anchoring protein.
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| Abstract |
In many non-excitable cells, the predominant mode of agonist-activated Ca(2+) entry switches from the arachidonic acid-regulated Ca(2+) (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.
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| Authors | Olivier Mignen, Jill L Thompson, Trevor J Shuttleworth |
| Journal | The Journal of physiology (J Physiol) Vol. 567 Issue Pt 3 Pg. 787-98 (Sep 15 2005) ISSN: 0022-3751 [Print] England |
| PMID | 15994185 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
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