THE ROLE OF PLASMA-MEMBRANE K-CELLS( AND CA2+ PERMEABILITIES FOR GLUCOSE INDUCTION OF SLOW CA2+ OSCILLATIONS IN PANCREATIC BETA)

In individual pancreatic beta-cells the rise of the cytoplasmic Ca2+ c oncentration ([Ca2+](i)), induced by 11 mM glucose, is manifested eith er as oscillations (0.2-0.5 min(-1)) or as a sustained elevation. The significance of the plasma membrane permeability of Ca2+ and K+ for th e establishment of these slow oscillations was investigated by dual wa velength microfluorometric measurements of [Ca2+](i) in individual ob/ ob mouse beta-cells loaded with fura-2. Increasing the extracellular C a2+ to 10 mM or the addition of Ca2+ channel agonist BAY K 8644 (1 mu M) or K+ channel blocker tetraethylammonium(+) (TEA; 10-20 mM) caused steeper rises and higher peaks of the glucose-induced oscillations. Ho wever, when extracellular Ca2+ was lowered to 0.5 mM the oscillations were transformed into a sustained suprabasal level. When the beta-cell s exhibited glucose-stimulated sustained elevation of [Ca2+](i) in the presence of a physiological Ca2+ concentration (1.3 mM), it was possi ble to induce slow oscillations by prompting the entry of Ca2+ either by raising the extracellular Ca2+ concentration to 10 mM or adding TEA or BAY K 8644. The results indicate that glucose-induced slow oscilla tions of [Ca2+](i) depend on the closure of ATP-regulated K+ channels and require that the rate of Ca2+ influx exceeds a critical level. Apa rt from an inherent periodicity in ATP production it is proposed that Ca2+-induced ATP consumption in the submembrane space contributes to t he cyclic changes of the membrane potential determining periodic entry of Ca2+.