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 preparations7–9 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.