DEPLETION OF INTRACELLULAR CALCIUM STORES TRIGGERS TRANSPLASMAMEMBRANE CHLORIDE INFLUX IN HUMAN-LYMPHOCYTES - REGULATION BY TYROSINE KINASE

The capacitative regulation of intracellular chloride concentration ([ Cl-](i)) was measured in intact human lymphocytes using the Cl--sensit ive fluorescence dye 6-methoxy-1-(3-sulfonato-propyl)-quinolinium (SPQ ). The fluorescence was measured at 433 nm with. the excitation wavele ngth of 344 nm. The emptying of intracellular Ca2+ stores after the sp ecific inhibition of the endoplasmic Ca2+ ATPase by thapsigargin produ ced a concentration-dependent transplasmamembrane Cl- influx. The thap sigargin-induced Cl- increase was also seen in the absence of extracel lular Ca2+, but it was significantly reduced after the addition of the Cl- exchange blocker, 4,4'-diisothiocyanostilbene-2,2'-disulfonic aci d. The thapsigargin-induced Cl- increase was significantly reduced aft er the specific inhibition of tyrosine kinase by genistein or tyrphost in A25. It is concluded that the depletion of intracellular Ca2+ pools triggers transplasmamembrane Cl- influx by a tyrosine kinase-dependen t mechanism. (C) 1995 Academic Press, Inc.