Opposite effects of indacrinone (MK-196) on sodium and chloride conductance of amphibian skin

Abstract

Indacrinone, a drug chemically related to ethacrynic acid, usually stimulated reversibly short circuit current and sodium influx when applied to the epithelial surface of amphibian skin. Concomitantly, transepithelial conductance, gt, decreased, provided chloride was the main anion in the incubation fluid. Electrophysiological analysis including microelectrode impalement indicated that the drug increased the sodium-conductance at the apical border of the impaled (most likely granular) cells. The decrease in gt thus points at shunt conductance being reduced with indacrinone, sometimes drastically. Decrease of transepithelial chloride flux with the drug as well as lack of effect of the drug on gt in the absence of chloride on the epithelial side demonstrate the influence of indacrinone on a chloride specific pathway. Whether this is along a paracellular route or through a cellular compartment not coupled to granular cells (mitochondria-rich cells?) cannot be decided on the basis of the present data.