Effects of chloride deficiency on the pancreatic B-cell response to acetylcholine.
Muscarinic stimulation of pancreatic B-cells markedly amplifies insulin secretion through complex mechanisms which involve changes in membrane potential and ionic fluxes. In this study, normal mouse islets were used to evaluate the role of Cl- ions in these effects of acetylcholine (ACh). Whatever the concentration of glucose, the rate of 36Cl- efflux from islet cells was unaffected by ACh. Replacement of Cl- by impermeant isethionate in a medium containing 15 mM glucose did not affect, or only slightly decreased, the ability of ACh to depolarize the B-cell membrane and increase electrical activity, to accelerate 45Ca2+ and 86Rb+ efflux from islet cells, and to amplify insulin release. In the absence of extracellular Ca2+, a high concentration of ACh (100 microM) mobilized intracellular Ca2+ and caused a transient release of insulin and a sustained acceleration of 86Rb+ efflux. None of these effects was affected by Cl- omission or by addition of furosemide, a blocker of the Na+, K+, 2Cl- cotransport. Isethionate substitution for Cl- in a medium containing a nonstimulatory concentration of glucose (3 mM) barely reduced the depolarization of B-cells by ACh, but inhibited the concomitant increase in 86Rb+ efflux. We have no explanation for the latter effect that was not mimicked by furosemide. In conclusion, ACh stimulation of pancreatic B-cells, unlike that of exocrine acinar cells, is largely independent of Cl- and is insensitive to furosemide. The acceleration of ionic fluxes produced by ACh does not involve the Na+, K+, 2Cl- cotransport system.
Hermans
M P
MP
Unité de Diabétologie et Nutrition, University of Louvain, Faculty of Medicine, Brussels, Belgium.
Schmeer
W
W
Gérard
M
M
Henquin
J C
JC
D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002132:Calcium Radioisotopes / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D002712:Chlorides / Q000494:pharmacology / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D012414:Rubidium Radioisotopes / Q000378:metabolism
D002132:Calcium Radioisotopes; D002712:Chlorides; D007328:Insulin; D012414:Rubidium Radioisotopes; D005665:Furosemide; D005947:Glucose; D000109:Acetylcholine; D002118:Calcium