DEPLETION OF INSP3 STORES ACTIVATES A CA2+ AND K+ CURRENT BY MEANS OFA PHOSPHATASE AND A DIFFUSIBLE MESSENGER

IN non-excitable cells, release of Ca2+ from the inositol 1,4,5-trisph osphate (InsP3)-sensitive store can activate Ca2+ entry1-3. Very littl e is known about the signal mechanism relating store emptying to plasm a membrane Ca2+ influx. It has been suggested that the signal may be e ither a diffusible messenger like an inositol phosphate4, or the InsP3 receptor itself, which, by physically coupling to some component of C a2+ entry in the plasma membrane, may link store release to Ca2+ entry 5. The nature of the Ca2+ entry pathway is also unclear. Only in mast cells has a very selective Ca2+ current been observed after store empt ying6. Activation of exogenous 5-hydroxytryptamine (5-HT) receptors ex pressed in Xenopus oocytes or direct injection of InsP3 evokes Ca2+ en try activated by InsP3 pool depletion7. Here we investigate the nature of this influx pathway and find a current activated by pool depletion . This has an unusual selectivity in that it is more permeable to Ca2 ions than to other divalent cations (Ba2+, Sr2+ or Mn2+). Moreover, a K+ permeability is also stimulated after pool depletion. The activati on of this store depletion current involves both a phosphatase and an unidentified diffusible messenger. Both the Ca2+ entry pathway and the activating factors found here may be relevant to pool-depleted Ca2+ e ntry in a variety of non-excitable cells.