ACETAZOLAMIDE SLOWS DOWN THE GLUCOSE-INDUCED MEMBRANE DEPOLARIZATION IN PANCREATIC B-CELLS: THE H+-SENSITIVE K+-PERMEABILITY IS RESPONSIBLE FOR THE DEPOLARIZATION

Abstract

Effects of a carbonic anhydrase inhibitor, acetazolamide, on the electrical activities of mouse pancreatic B-cells were examined using the conventional microelectrode technique. Acetazolamide inhibits the hydration process of CO2, and is therefore expected to suppress the H+ production in B-cells without affecting the ATP production. The depolarization rate in the pre-spike-train phase was elevated depending on the glucose concentration in the medium. In the presence of acetazolamide (1 .times. 10-4 M), the depolarization rate was about a half of its control value at all glucose concentrations examined. The rate of the depolarization induced by removing external Na+ was also glucose-dependent and suppressed by acetazolamide. Even in a nominally Ca2+-free medium, the removal of the external Na+ caused a depolarization. This finding indicates that ions other than Ca2+ and Na+ carry the background inward current under these conditions. The suppression of Cl-/HCO3- exchange resulted in a small hyperpolarization, suggesting that the suppression of the extrusion of HCO3-, another product of CO2 hydration, induces an intracellular alkalization. These findings support the view that a decrease in the H+-sensitive K+-permeability is responsible for the physiological depolarization observed when raising the glucose concentration in the medium.