STORE DEPLETION AND CALCIUM INFLUX

Calcium influx in nonexcitable cells regulates such diverse processes as exocytosis, contraction, enzyme control, gene regulation, cell prol iferation, and apoptosis. The dominant Ca2+ entry pathway in these cel ls is the store-operated one, in which Ca2+ entry is governed by the C a2+ content of the agonist-sensitive intracellular Ca2+ stores. Only r ecently has a Ca2+ current been described that is activated by store d epletion. The properties of this new current, called Ca2+ release-acti vated Ca2+ current (I-CRAC), have been investigated in detail using th e patch-clamp technique. Despite intense research, the nature of the s ignal that couples Ca2+ store content to the Ca2+ channels in the plas ma membrane has remained elusive. Although I-CRAC appears to be the mo st effective and widespread influx pathway, other store-operated curre nts have also been observed. Although the Ca2+ release-activated Ca2channel has not yet been cloned, evidence continues to accumulate that the Drosophila trp gene might encode a store-operated Ca2+ channel. I n this review, we describe the historical development of the field of Ca2+ signaling and the discovery of store-operated Ca2+ currents. We f ocus on the electrophysiological properties of the prototype store-ope rated current I-CRAC, discuss the regulatory mechanisms that control i t, and finally consider recent advances toward the identification of m olecular mechanisms involved in this ubiquitous and important Ca2+ ent ry pathway.