Extracellular Ca2+ per se inhibits quantal size of catecholamine release in adrenal slice chromaffin cells

Classic calcium hypothesis states that depolarization-induced increase in intracellular Ca2+ concentration ([Ca2+]) triggers vesicle exocytosis by increasing vesicle release probability in neurons and neuroendocrine cells. The extracellular Ca2+, in this calcium hypothesis, serves as a reservoir of Ca2+ source. Recently we find that extracellular Ca2+ per se inhibits the [Ca2+], dependent vesicle exocytosis, but it remains unclear whether quantal size is regulated by extracellular, or intracellular Ca2+ or both [1]. In this work we showed that, in physiological condition, extracellular Ca2+ per se specifically inhibited the quantal size of single vesicle release in rat adrenal slice chromaffin cells. The extracellular Ca2+ in physiological concentration (2.5 mM) directly regulated fusion pore kinetics of spontaneous quantal release of catecholamine. In addition, removal of extracellular Ca2+ directly triggered vesicle exocytosis without eliciting intracellular Ca2+. We propose that intracellular Ca2+ and extracellular Ca2+ per se cooperately regulate single vesicle exocytosis. The vesicle release probability was jointly modulated by both intracellular and extracellular Ca2+, while the vesicle quantal size was mainly determined by extracellular Ca2+ in chromaffin cells physiologically. (C) 2014 Elsevier Ltd. All rights reserved.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000342889900009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Cell BiologySCI(E)1ARTICLEweibear@gmail.com; Liu_Tao@sbic.a-star.edu.sg; zzhou@pku.edu.cn3202-2075