Ta. Kinard et Ls. Satin, AN ATP-SENSITIVE CL- CHANNEL CURRENT THAT IS ACTIVATED BY CELL SWELLING, CAMP, AND GLYBURIDE IN INSULIN-SECRETING CELLS, Diabetes, 44(12), 1995, pp. 1461-1466
Citations number
56
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Although chloride ions are known to modulate insulin release and islet
electrical activity, the mechanism or mechanisms mediating these effe
cts are unclear. However, numerous studies of islet Cl- fluxes have su
ggested that Cl- movements are glucose and sulfonylurea sensitive and
are blocked by stilbene-derivative Cl- channel blockers. We now show f
or the first time that insulin-secreting cells have a Cl- channel curr
ent, which we term I-Cl,I-islet. The current is activated by hypotonic
conditions, 1-10 mu mol/l glyburide and 0.5 mmol/l 8-bromoadenosine 3
':5'-cyclic monophosphate sodium, I-Cl,I-islet is mediated by Cl- chan
nels, since replacing [Cl-](0) with less permeant aspartate reduces cu
rrent amplitude and depolarizes its reversal potential, In addition, 1
00 mu mol/l 4,4'-diisothio-cyanatostilbene-2,2'-disulfonic acid (DIDS)
or glyburide, which blocks the Cl- channels of other cell types, bloc
k I-Cl,I-islet. Reducing [ATP], 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 similar to
0 mV, At potentials associated with the silent phase of islet electric
al activity (approximately -65 mV), I-Cl,I-islet mediates a large inwa
rd current, which would be expected to depolarize islet membrane poten
tial, Thus, activation of this novel current by increased intracellula
r cAMP, sulfonylureas, or ATP may contribute to the well-known depolar
izing effects of these agents.