DEPLETED INTERNAL STORE-ACTIVATED CA2+ ENTRY CAN TRIGGER NEUROTRANSMITTER RELEASE IN BOVINE CHROMAFFIN CELLS

A potential role of the intracellular Ca2+ stores in modulating catech olamine release has been investigated in bovine chromaffin cells maint ained in tissue culture. Pharmacological depletion of the stores with a combination of caffeine, histamine and thapsigargin in Ca2+-free med ia resulted in a significantly greater release of catecholamines on re -exposure to Ca2+-containing media compared with that from non-store d epleted cells. The increase in catecholamine release was prevented by intracellular BAPTA indicating that the increase was caused by a rise in Ca2+. Measurement of intracellular free Ca2+ concentration with the fluorescent indicator, fura-2, over the same time-course as the catec holamine release experiments showed that upon restoration of external Ca2+ there was an immediate, substantial and maintained increase in cy tosolic Ca2+. It is most probable that the increase in catecholamine r elease was a consequence of an increase in Ca2+ influx triggered by pr ior depletion of the internal Ca2+ stores. However, the data suggest t hat capacitative Ca2+ entry is poorly linked to catecholamine release; although;Ca2+ entry on restoration of external Ca2+ was immediate and substantial, the increase in catecholamine release, although quantita tively significant, was slowly realised.