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: Alexandria, VA American Diabetes Association 01.12.1995
• Subjects: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology; 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Adenosine Triphosphate - pharmacology; Animals; Biological and medical sciences; Cell Line; Cell Size - physiology; Chloride Channels - drug effects; Chloride Channels - physiology; Cyclic AMP - pharmacology; Electric Conductivity; Endocrine pancreas; Fundamental and applied biological sciences. Psychology; Glibenclamide; Glyburide; Glyburide - pharmacology; Hormones. Régulation; Hypotonic Solutions; Insulin - metabolism; Insulin Secretion; Mice; Pancreatic beta cells; Physiological aspects; Vertebrates: endocrinology; Pancreatic hormone; Langerhans islet; Rodentia; Cyclic AMP; Ionic channel; Ionic current; Insulin; Vertebrata; Mammalia; B-Cell; Mouse; Chlorides; ATP; Endocrine pancreas
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.44.12.1461

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.