Cation transport by pancreatic beta-cells: effect of 4-aminopyridine on 86Rb+ and 45Ca2+ fluxes.

The effects of 4-aminopyridine (4-AP) on insulin release, glucose oxidation and 86Rb+ and 45Ca2+ fluxes of rat isolated islets were studied. 4-AP (0.1 and 1.0 mM) did not alter the 86Rb+ fractional efflux. However, 10 mM 4-AP significantly increased the 86Rb+ fractional efflux. 10 mM 4-AP also reduced the insulin release from islets incubated over 90 min in the presence of both 6 and 16.7 mM glucose and from perifused islet in the presence of 16.7 mM glucose. 4-AP (10 mM) only transiently increased the insulin release and the 45Ca2+ fractional efflux in the presence of 6 mM glucose. The 45Ca2+ fractional efflux was not changed when the islets were perifused at higher glucose concentration. At zero, 6 or 16.7 mM glucose, 4-AP (10 mM) significantly increased the 45Ca2+ net uptake by islets incubated for 90 min. 10 mM 4-AP significantly reduced the glucose oxidation of islets incubated for 120 min in the presence of 16.7 mM glucose. The effects of 10 mM 4-AP on the dynamics of insulin release and 86Rb+ fractional efflux were poorly reversible. In conclusion, 4-AP, at concentrations that did not alter the glucose metabolism, (0.1 and 1 mM), failed to affect the K+ permeability in beta-cells as judged by the measurements of 86Rb+ fractional efflux. At higher concentrations (10 mM) 4-AP increased 86Rb+ efflux, decreased glucose metabolism and reduced insulin release.