Binding sites related to ouabain-induced stimulation or inhibition of the sodium pump

Abstract

THE concentration of free cardiac glycosides in the blood of patients treated for heart failure ranges between 1 and 5 nM (refs 1–3). Studies on human heart slices have shown that, within this range of concentrations, digitoxin does not inhibit the sodium pump but does stimulate ⁴²K uptake³. Similar observations have been made with isolated guinea pig atria: low concentrations of ouabain (near 1 nM) stimulate ⁴²K uptake whereas higher concentrations inhibit it⁴. These results are in agreement with recent electrophysiological observations on Purkinje fibres showing that low doses of ouabain produce changes in the K gradient that reflect stimulation of the sodium pump⁵. It has also been observed that the stimulation of the sodium pump by ouabain is associated with a positive ionotropic effect⁶. Earlier studies with guinea pig atria⁴ and other preparations^7–9 showed that the binding of ouabain occurs on non-specific and specific sites. The specific binding is fitted by a Langmuir curve with an equilibrium constant close to that estimated by measuring the inhibition of the sodium pump. We report here the existence of a binding with a higher affinity associated with the stimulation of the sodium pump.