ELECTROPHYSIOLOGICAL EVIDENCE FOR THE INHIBITION OF POTASSIUM PERMEABILITY IN PANCREATIC β‐CELLS BY GLIBENCLAMIDE

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Abstract
The effects of glibenclamide on the electrical activity of the .beta.-cells of the islets of Langerhans of normal mice were investigated in the absence and presence of glucose (11.1 mM). Glibenclamide depolarized the cell membrane and this was interpreted in terms of an increase in the ratio of the Na+ and K+ permeabilities, PNa/PK. This ratio increased from 0.05 to 0.24 in the presence of 4 .mu.M glibenclamide and zero glucose. The input resistance of the .beta.-cells also increased. These observations indicate a decrease in K+ permeability. The effect is only slowly reversed after removal of glibenclamide. Uncouplers of oxidative phosphorylation do not reverse the depolarization induced by glibenclamide. Glibenclamide is acting directly to inhibit the [Ca2+]i[intracellular Ca]-gated K+ permeability in the .beta.-cell membrane.