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In electrically non-excitable cells, Ca2+ entry is mediated predominantly through the store-operated Ca2+ influx pathway, which is activated by emptying the intracellular Ca2+ stores following an increase in the levels of the second messenger inositol 1,4,5-trisphophate (InsP3). InsP3 is generated from the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2). Recently, roles for other phosphoinositides (PIs) in store-operated Ca2+ influx have been suggested because inhibitors of PI kinases reduce Ca2+ influx when the latter is triggered independent of PIP2 hydrolysis. Using the whole-cell patch-clamp technique to record the store-operated Ca2+ current ICRAC in RBL-1 cells, we examined whether PIs are involved in linking store depletion to activation of CRAC channels. Of several structurally distinct PI kinase inhibitors, only one (LY294002) was able to reduce partially the extent of activation of ICRAC although this could not be reversed by exogenous phosphatidylinositol 3,4,5-trisphosphate (PIP3). Our findings suggest that, if a PI kinase is involved in activation of ICRAC in RBL-1 cells, it has a unique pharmacological profile. Alternative explanations for the results are discussed.

Type

Journal article

Journal

Pflugers Arch

Publication Date

06/2001

Volume

442

Pages

391 - 395

Keywords

1-Phosphatidylinositol 4-Kinase, Androstadienes, Animals, Calcium, Chromones, Enzyme Inhibitors, Leukemia, Basophilic, Acute, Morpholines, Patch-Clamp Techniques, Phosphatidylinositol 3-Kinases, Phosphatidylinositol 4,5-Diphosphate, Phosphatidylinositol Phosphates, Quercetin, Rats, Staurosporine, Tumor Cells, Cultured, Wortmannin