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I. Physiologisches Institut und Medizinische Klinik, Universität des Saarlandes, 6650 Homburg/Saar, Federal Repulic of Germany
1. The contribution of the sodium pump to the membrane potential of mouse pancreatic B-cells was studied with micro-electrodes.
2. In 0 or 3 mM-glucose, ouabain rapidly (within 2 min) depolarized the B-cell membrane by an average of 7 mV, whereas K omission hyperpolarized it markedly.
3. In 6 or 7 mM-glucose, ouabain still produced depolarization, but K omission had no consistent effect. Both induced electrical activity in certain cells.
4. In 10 mM-glucose, withdrawal of ouabain or K re-introduction caused a transient hyperpolarization with suppression of electrical activity. Duration and amplitude of the hyperpolarization increased with the time of pump blockade and with the concentration of ouabain.
5. The hyperpolarization following K re-admission was abolished by ouabain and that following ouabain withdrawal was prevented by K omission. Re-admission of various K concentrations showed that the hyperpolarization was not due to depletion of K just outside of the membrane.
6. In 10 mM-glucose, the membrane potential of B-cells exhibited repetitive slow waves with bursts of spikes on the plateau. These electrical events were modified by ouabain in a dose-dependent manner. The frequency of the slow waves augmented markedly because of an increase in the slope of the pre-potential and a shortening of the intervals; the slope of their repolarization phase decreased, but their duration was not changed.
7. Omission of K increased the slope of the pre-potential and the frequency of the slow waves. It also accelerated their repolarization phase and reduced their duration, likely because of the increase in driving force for K efflux. Increasing K concentration to 8 mM slowed the repolarization phase and lengthened the slow waves without changing their frequency.
8. Even when K permeability of the B-cell membrane was increased by high extracellular Ca, ouabain and K omission augmented the frequency of the slow waves.
9. In 0 or 10 mM-glucose, ouabain increased 86Rb+ efflux from perifused islets, whereas K omission decreased it. In 10 mM-glucose, a marked decrease in 86Rb+ efflux accompanied ouabain withdrawal and K re-introduction. The hyperpolarization is thus not due to an increase in K permeability.
10. It is concluded that, in pancreatic B-cells, the sodium pump is truly electrogenic, contributes to the resting potential and modulates the slow waves of membrane potential induced by glucose. Rapid changes in insulin release occurring upon inhibition or activation of the sodium pump may thus be due to the changes in B-cell membrane potential.
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