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 currentI _ARC (forarachidonate-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.

SK3/TRPC1/Orai1 complex regulates SOCE- dependent colon cancer cell migration: a novel opportunity to modulate Anti- EGFR mAb action by the alkyl-lipid Ohmline