Dual Effects of Na/K Pump Inhibition on Cytoplasmic Ca2+ Oscillations in Pancreatic β-Cells

Inhibition of the Na/K pump by ouabain or removal of K+ resulted in gradual increase of intracellular sodium in β-cell-rich pancreatic islets from ob/ob-mice exposed to 3 mM glucose. In individual β-cells this action of ouaham was paralleled by closure of ATP-regulated K+ channels and a slow elevation of the cytoplasmic Ca2+ concentration ([Ca2+]i). In most β-cells an increase of the glucose concentration to 11-20 mM induced large amplitude oscillations of [Ca2+]i, with a frequency of 0.2-0.5/min. Ouabain had dual actions on these glucose-induced oscillations in promoting their appearance and at higher concentrations transforming them into a sustained increase of [Ca2+]i. At 100 μM onabain reduced the frequency of the glucose-induced oscillations but nevertheless raised the time-average [Ca2+]i, by increasing the amplitudes and half-widths of the Ca2+ peaks. When high concentrations of ouabain or removal of K+ transformed the oscillations into a sustained increase of [Ca2+]i, the level reached exceeded that obtained in response to rise of glucose alone. By favoring Ca2+ entry and counteracting removal of the cation from the cytoplasm, Na/K pump inhibition perturbs the balance between the processes determining glucose-induced oscillations of [Ca2+]i.