Termination of cytosolic Ca² signals: Ca² reuptake into intracellular stores is regulated by the free Ca² concentration in the store lumen.

Mogami, Hideo; Tepikin, Alexei V.; Petersen, Ole H.

The mechanism by which agonist-evoked cytosolic Ca2 signals are terminated has been investigated. We measured the Ca2 concentration inside the endoplasmic reticulum store of pancreatic acinar cells and monitored the cytoplasmic Ca2 concentration by whole-cell patch-clamp recording of the Ca2 -sensitive currents. When the cytosolic Ca2 concentration was clamped at the resting level by a high concentration of a selective Ca2 buffer, acetylcholine evoked the usual depletion of intracellular Ca2 stores, but without increasing the Ca2 -sensitive currents. Removal of acetylcholine allowed thapsigargin­sensitive Ca2 reuptake into the stores, and this process stopped when the stores had been loaded to the pre-stimulation level. The apparent rate of Ca2 reuptake decreased steeply with an increase in the Ca2 concentration in the store lumen and it is this negative feedback on the Ca2 pump that controls the Ca2 store content. In the absence of a cytoplasmic Ca2 clamp, acetylcholine removal resulted in a rapid return of the elevated cytoplasmic Ca2 concentration to the pre-stimulation resting level, which was attained long before the endoplasmic reticulum Ca2 store had been completely refilled. We conclude that control of Ca2 reuptake by the Ca2 concentration inside the intracellular store allows precise Ca2 signal termination without interfering with store refilling.

CALCIUM channels; CELLULAR signal transduction; CELLULAR control mechanisms; PANCREATIC acinar cells; ENDOPLASMIC reticulum; CYTOPLASM

EMBO Journal, 1998, Vol 17, Issue 2, p435

0261-4189

Academic Journal

10.1093/emboj/17.2.435