I(ARC), a novel arachidonate-regulated, noncapacitative Ca2+ entry channel

Abstract

Along with the inositol trisphosphate-induced release of stored Ca2+, a receptor-enhanced entry of Ca2+ is a critical component of intracellular Ca2+ signals generated by agonists acting at receptors coupled to the activation of phospholipase C. Although the simple emptying of the intracellular Ca2+ stores is known to be capable of activating Ca2+ entry via the so-called 'capacitative' mechanism, recent evidence suggests that Ca2+ entry at physiological agonist concentrations, where oscillatory Ca2+ signals are typically observed, does not conform to such a model. Instead, a noncapacitative Ca2+ entry pathway regulated by arachidonic acid appears to be responsible for Ca2+ entry under these conditions. Using whole-cell patch clamp techniques we demonstrate that low concentrations of arachidonic acid activate a Ca2+-selective current that is superficially similar to the store-operated current I(CRAC), but which also demonstrates certain distinct features. We have named this novel current I(ARC) (for arachidonate-regulated calcium current). Importantly, I(ARC) can be readily activated in cells whose Ca2+ stores have been maximally depleted. I(ARC) represents a novel Ca2+ entry pathway that is entirely separate from those activated by store depletion and is specifically activated at physiological levels of stimulation.