The role of plasma membrane K + and Ca 2+ permeabilities for glucose induction of slow Ca 2+ oscillations in pancreatic β-cells

Abstract

In individual pancreatic β-cells the rise of the cytoplasmic Ca 2+ concentration ([Ca 2+] 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 Ca 2+ and K + for the establishment of these slow oscillations was investigated by dual wavelength microfluorometric measurements of [Ca 2+] i in individual ob/ob mouse-β-cells loaded with fura-2. Increasing the extracellular Ca 2+ to 10 mM or the addition of Ca 2+ channel agonist BAY K 8644 (1 μM) or K + channel blocker tetraethylammonium + (TEA; 10–20 mM) caused steeper rises and higher peaks of the glucose-induced oscillations. However, when extracellular Ca 2+ was lowered to 0.5 mM the oscillations were transformed into a sustained suprabasal level. When the β-cells exhibited glucose-stimulatedsustained elevation of [Ca 2+] i in the presence of a physiological Ca 2+ concentration (1.3 mM), it was possible to induce slow oscillations by promoting the entry of Ca 2+ either by raising the extracellular Ca 2+ concentration to 10 mM or adding TEA or BAY K 8644. The results indicate that glucose-induced slow oscillations of [Ca 2+] i depend on the closure of ATP-regulated K + channels and require that the rate of Ca 2+ 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 Ca 2+.