An ATP-sensitive Cl- channel current that is activated by cell swelling, cAMP, and glyburide in insulin-secreting cells

• Published in: Diabetes (New York, N.Y.) Vol. 44; no. 12; pp. 1461 - 1466
• Main Authors: Kinard, T. A., Satin, L. S.
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01.12.1995
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.44.12.1461

An ATP-sensitive Cl- channel current that is activated by cell swelling, cAMP, and glyburide in insulin-secreting cells. T A Kinard and L S Satin Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0524, USA. Abstract Although chloride ions are known to modulate insulin release and islet electrical activity, the mechanism or mechanisms mediating these effects are unclear. However, numerous studies of islet Cl- fluxes have suggested that Cl- movements and glucose and sulfonylurea sensitive and are blocked by stilbene-derivative Cl- channel blockers. We now show for the first time that insulin-secreting cells have a Cl- channel current, which we term ICl,islet. The current is activated by hypotonic conditions, 1-10 mumol/l glyburide and 0.5 mmol/l 8-bromoadenosine 3':5'-cyclic monophosphate sodium. ICl,islet is mediated by Cl- channels, since replacing [Cl-]o with less permeant aspartate reduces current amplitude and depolarizes its reversal potential. In addition, 100 mumol/l 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) or glyburide, which blocks the Cl- channels of other cell types, block ICl,islet. Reducing [ATP]i reduces the amplitude of the current, suggesting that it may be under metabolic control. The current is time-independent and shows strong outward-rectification beyond approximately 0 mV. At potentials associated with the silent phase of islet electrical activity (approximately -65 mV), ICl,islet mediates a large inward current, which would be expected to depolarize islet membrane potential. Thus, activation of this novel current by increased intracellular cAMP, sulfonylureas, or ATP may contribute to the well-known depolarizing effects of these agents.