Effects of Cl- deficiency on the membrane potential in mouse pancreatic beta-cells.

The membrane potential of mouse pancreatic beta-cells was measured with microelectrodes. In the resting cell (3 mM D-glucose), the membrane potential was -63 +/- 3 mV (mean +/- S.E. for four experiments). In the presence of 3 mM D-glucose, total Cl- substitution by isethionate induced a depolarization by 3-4 mV, and readmission of Cl- induced a hyperpolarization by 3-5 mV. At 10 mM glucose, reduction of Cl- to 12 mM by substituting isethionate for Cl- reversibly shifted the repolarization potential by 6-9 mV in the positive direction and stimulated the burst activity during the initial 2-3 min by increasing the fraction of plateau phase. This was followed by a gradual inhibition of electrical activity, including decrease in fraction of plateau phase and slow wave amplitude. Total substitution of Cl- by isethionate or methyl sulphate reversibly shifted the repolarization potential by 3-4 mV in the positive direction and rapidly inhibited the electrical burst pattern without any initial stimulation. Glucose-induced (10 mM) insulin release (15 min) and 45Ca2+ uptake (3 min) were strongly inhibited by reducing the Cl- concentration to 10 mM (isethionate as substitute) and were further inhibited by further reduction of the Cl- concentration. It is suggested that beta-cells are equipped with on electrogenic Cl- flux, which can affect the burst pattern of electrical activity. The inhibitory effects of Cl- substitution may be explained by an influence of Cl- on the voltage-controlled Ca2+ channels.