AGONIST-RELEASABLE INTRACELLULAR CALCIUM STORES AND THE PHENOMENON OFSTORE DEPENDENT CALCIUM-ENTRY - A NOVEL HYPOTHESIS BASED ON CALCIUM STORES IN ORGANELLES OF THE ENDOCYTOTIC AND EXOCYTOTIC APPARATUS

Store-dependent calcium entry represents a little characterized calciu m permeation pathway that is present in a variety of cell types. It is activated in an unknown way by depletion of intracellular calcium sto res, for example in the course of phospholipase C stimulation. Current hypotheses propose that depleted calcium stores signal their filling state to this permeation pathway either by direct, protein-mediated in teraction or by release of a small, diffusible messenger. The further characterization of store-dependent calcium entry will benefit from pr ogress in the identification of the intracellular calcium storing comp artments. Recent findings reviewed exocytosis. This commentary describ es a novel model of store-dependent calcium entry based on calcium sto res belonging to the endo- and exocytotic organelle system. Such calci um stores could establish a tubule-like connection with the extracellu lar space, in analogy to the cellular compartments that contain the in sulin-sensitive glucose transporter or the gastric proton pump. This c onnection will provide a pathway for store-dependent calcium entry. Un der store depletion, extracellular calcium will permeate through the t ubule-like connection into the store lumen and from there into the cyt osol. The consequences of this model for the development of drugs modu lating store-dependent calcium entry are discussed.