Modulation of Ca2+ and K+ permeabilities by oxotremorine-m (Oxo-m) in rodent pancreatic B-cells.
The effects of the muscarinic agonist oxotremorine-m (Oxo-m) on 45Ca and 86Rb fluxes, insulin secretion, cytoplasmic Ca2+ concentration ([Ca2+]i) and membrane potential in pancreatic B-cells were studied. Oxo-m (40-200 microM) increased the [Ca2+]i by about 250 nM, irrespective of the glucose concentration present in the medium (2.8-22 mM). This effect was reduced by 50% upon the addition of EGTA. Oxo-m (50 microM) increased the 45Ca efflux from islets perifused in the absence or presence of [Ca2+]o, although under the former condition this efflux was transient. The difference between effluxes measured in the absence and presence of [Ca2+]o represents the sustained second component, which presumably reflects Ca2+ influx. In both the absence and presence of 11.2 mM glucose. Oxo-m (50 microM) transiently increased 86Rb efflux. In the presence of glucose, Oxo-m provoked a transient polarization of the B-cell membrane associated with an increase in the K+ permeability values. K+ permeability returned to basal values (no Oxo-m) after 1-2 min. These results indicate that the initial phase of Oxo-m-induced insulin secretion depends partially on intracellular Ca2+ release, and that the sustained enhancement of release depends on Ca2+ influx. The participation of a calcium release-activated current (ICRAC) is proposed to explain the sustained small changes in membrane potential.
Bordin
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Departamento de Fisiologia e Biofísica, Instituto de Biologia, UNICAMP, Brazil.
Carneiro
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Boschero
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002463:Cell Membrane Permeability / Q000187:drug effects; D004533:Egtazic Acid / Q000494:pharmacology; D004594:Electrophysiology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010095:Oxotremorine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D012414:Rubidium Radioisotopes
D002132:Calcium Radioisotopes; D007328:Insulin; D018721:Muscarinic Agonists; D012414:Rubidium Radioisotopes; D004533:Egtazic Acid; D010095:Oxotremorine; D005947:Glucose; D011188:Potassium; D002118:Calcium