Referenced in: none

Automatically associated channels: ClC3 , ClC4

Title: Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification.

Authors: S Barg, P Huang, L Eliasson, D J Nelson, S Obermüller, P Rorsman, F Thévenod, E Renström

Journal, date & volume: J. Cell. Sci., 2001 Jun , 114, 2145-54

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11493650

Abstract
ATP-dependent priming of the secretory granules precedes Ca(2+)-regulated neuroendocrine secretion, but the exact nature of this reaction is not fully established in all secretory cell types. We have further investigated this reaction in the insulin-secreting pancreatic B-cell and demonstrate that granular acidification driven by a V-type H(+)-ATPase in the granular membrane is a decisive step in priming. This requires simultaneous Cl(-) uptake through granular ClC-3 Cl(-) channels. Accordingly, granule acidification and priming are inhibited by agents that prevent transgranular Cl(-) fluxes, such as 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and an antibody against the ClC-3 channels, but accelerated by increases in the intracellular ATP:ADP ratio or addition of hypoglycemic sulfonylureas. We suggest that this might represent an important mechanism for metabolic regulation of Ca(2+)-dependent exocytosis that is also likely to be operational in other secretory cell types.