Suppression of Ca syntillas increases spontaneous exocytosis in mouse adrenal chromaffin cells

Since the work of Katz, Douglas, and their collaborators almost half a century ago (Katz, 1969), a central concept in the physiology of neurosecretion is that a rise in cytosolic [Ca], resulting from Ca influx, triggers exocytosis. More recently it has become clear that the rise in [Ca] occurs in a microdomain within the vicinity (i.e., at a distance of 200–300 nm in chromaffin cells) of plasmalemmal Ca channels (García et al., 2006; Neher and Sakaba, 2008). This finding raises the possibility of other microdomains where a rise in focal [Ca] might mediate other processes, allowing Ca to subserve several functions without cross talk. This possibility receives further support from the study of Ca sparks in smooth muscle cells. Ca sparks are focal Ca transients found in striated and smooth muscle and mediated by RYRs (Cheng and Lederer, 2008). In striated muscle, they are the quanta or building blocks that make up a global increase in [Ca] to trigger contraction (Csernoch, 2007). However, in smooth muscle, Ca sparks have quite a different function. They activate large conductance Ca-activated K channels (BK channels) located within 150–300 nm of the spark site (ZhuGe et al., 2002); the resulting K efflux and hyperpolarization deactivates