MODULATION OF CA2-M (OXO-M) IN RODENT PANCREATIC B-CELLS( AND K+ PERMEABILITIES BY OXOTREMORINE)

The effects of the muscarinic agonist oxotremorine-m (Oxo-m) on Ca-45 and Rb-86 fluxes, insulin secretion, cytoplasmic Ca2+ concentration [C a2+](i) and membrane potential in pancreatic B-cells were studied. Oxo -m (40-200 mu M) increased the [Ca2(+)](i) by about 250 nM, irrespecti ve of the glucose concentration present in the medium (2.8-22 mM). Thi s effect was reduced by 50% upon the addition of EGTA. Oxo-m (50 mu M) increased the Ca-45 efflux from islets perifused in the absence or pr esence of [Ca2+](o), although under the former condition this efflux w as transient. The difference between effluxes measured in the absence and presence of [Ca2+](o) represents the sustained second component, w hich presumably reflects Ca2+ influx. In both the absence and presence of 11.2 mM glucose, Oxo-m (50 mu M) transiently increased Rb-86 efflu x. In the presence of glucose, Oxo-m provoked a transient polarization of the B-cell membrane associated with an increase in the K+ permeabi lity values. K+ permeability returned to basal values (no Oxo-m) after 1-2 min. These results indicate that the initial phase of Oxo-m-induc ed 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 (I-CRAC) is p roposed to explain the sustained small changes in membrane potential.