Active ion (NaCl) transport across isolated frog skin is discussed in relation to sodium and potassium composition and to O2 consumption of skin. A distinction is made between processes in skin related to "unidirectional active ion transport" and processes related to "maintenance electrolyte equilibrium;" i.e., ionic composition of skin. Several metabolic inhibitors were found that could be used in separating maintenance electrolyte equilibrium from unidirectional active ion transport. Fluoroacetate (up to 1 x 10–2M/liter) did not affect maintenance electrolyte equilibrium, but severely diminished the rate of active ion transport. This could also be accomplished with azide and diethyl malonate when 1 x 10–3 molar concentrations were used. When applied in higher concentrations, these two inhibitors, and several others, diminished active ion transport, but this was associated with changes in maintenance electrolyte equilibrium (gain of Na+ by and loss of K+ from skin). Similar observations were made when skins were subjected to K+-deficient media. Mersalyl and theophylline, in low concentrations, stimulated active ion transport without leading to changes in maintenance electrolyte equilibrium. Inhibition of active ion transport was found accompanied by decrease, increase, and unaltered over-all O2 consumption, depending on the kind of chemical agent used. A provisional scheme of the mechanism of unidirectional active ion transport is proposed. It is conceived as a process of metabolically supported ion exchange adsorption, involving a carrier, forming complexes with K+ and Na+, a trigger, K+ ions, and two spatially separated metabolic pathways.

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