An analysis of the actions of low concentrations of ouabain on membrane currents in Purkinje fibres.

Abstract

The influence of low concentrations (5 .times. 10-8 to 5 .times. 10-7 M) of ouabain on the K gradient in sheep cardiac Purkinje fibers was observed by measuring changes in the reversal potential for a K specific current, iK2, and by measuring total steady-state current-voltage relations. Provided that the bathing solution K concentration, [K]o was not too low, these doses of ouabain were often observed to increase the K gradient, i.e., the reversal potential was shifted in a negative direction. The change in the reversal potential and in the current-voltage relation could be mimicked by reducing the value of [K]o in the absence of ouabain. Ouabain may stimulate the Na+-K+ exchange pump and so reduce the K concentration, [K]e, in the clefts of the preparation. At sufficiently low values of [K]o a dose of ouabain that was stimulatory may become inhibitory. The reversal potential for iK2 then shifts in a positive direction. During either stimulation or inhibition, the speed of change of reversal potential is consistent with a change in [K]e, which may change fairly rapidly. It is not possible to account for the results solely by changes in intracellular concentration, [K]i. Low concentrations of ouabain have no effect on the activation curve, s.infin. (Em), controlling iK2. The changes in iK2 are solely attributable to changes in reversal potential. Since net stimulation of the Na+-K+ exchange pump was previously observed to occur at doses of ouabain that exert a strong positive inotropic action on Purkinje fibers, it is not likely that the inotropic action is causally related to net pump inhibition.