The role of plasma membrane K+ and Ca2+ permeabilities for glucose induction of slow Ca2+ oscillations in pancreatic beta-cells.

In individual pancreatic beta-cells the rise of the cytoplasmic Ca2+ concentration ([Ca2+]i), induced by 11 mM glucose, is manifested either 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 the establishment of these slow oscillations was investigated by dual wavelength microfluorometric measurements of [Ca2+]i in individual ob/ob mouse beta-cells loaded with fura-2. Increasing the extracellular Ca2+ to 10 mM or the addition of Ca2+ channel agonist BAY K 8644 (1 microM) or K+ channel blocker tetraethylammonium+ (TEA: 10-20 mM) caused steeper rises and higher peaks of the glucose-induced oscillations. However, when extracellular Ca2+ was lowered to 0.5 mM the oscillations were transformed into a sustained suprabasal level. When the beta-cells exhibited glucose-stimulated sustained elevation of [Ca2+]i in the presence of a physiological Ca2+ concentration (1.3 mM), it was possible to induce slow oscillations by promoting 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 oscillations of [Ca2+]i depend on the closure of ATP-regulated K+ channels and require that the rate of Ca2+ influx exceeds a critical level. Apart from an inherent periodicity in ATP production it is proposed that Ca(2+)-induced ATP consumption in the submembrane space contributes to the cyclic changes of the membrane potential determining periodic entry of Ca2+.