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The effects of glibenclamide on the electrical activity of the beta-cells of the islets of Langerhans of normal mice have been investigated in the absence and presence of glucose (11.1 mM). Glibenclamide depolarized the cell membrane and this has been 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 microM 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. It is suggested that glibenclamide is acting directly to inhibit the [Ca2+]i-gated K+ permeability in the beta-cell membrane.
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