Modulation of secretion by the endoplasmic reticulum in mouse chromaffin cells.

Abstract

The endoplasmic reticulum (ER) has been suggested to modulate secretion either behaving as a Ca2+ sink or as a Ca2+ source in neuronal cells. Working as a Ca2+ sink, through ER-Ca2+ pumping, it may reduce secretion induced by different stimuli. Instead, working as a Ca2+ source through the Ca2+ induced Ca2+ release (CICR) phenomenon, it may potentiate secretion triggered by activation of plasma membrane Ca2+ channels. We have previously demonstrated the presence of CICR in bovine chromaffin cells, but we now find that mouse chromaffin cells almost lack functional caffeine-sensitive ryanodine receptors in the ER and, consistently, no CICR from the ER could be observed. In addition, inhibition of ER Ca2+ pumping with ciclopiazonic acid or thapsigargin strongly stimulated high-K+-evoked catecholamine secretion and cytosolic [Ca2+] ([Ca2+]c) transients. Surprisingly, 5 mm caffeine reduced high-K+-induced [Ca2+]c peaks but considerably potentiated secretion induced by high-K+ stimulation. However, this potentiation was insensitive to ryanodine and additive to that induced by emptying the ER of Ca2+ with thapsigargin, suggesting that it is unrelated to the activation of ryanodine receptors. We conclude that, in mouse chromaffin cells, CICR is not functional and the ER strongly inhibits secretion by acting as a damper of the [Ca2+]c signal.