Diffusion characteristics dissociate ouabain binding from inotropic effect in guinea-pig myocardium.

1. [3H]-ouabain uptake in resting guinea-pig papillary muscles depended directly on incubation time and inversely with muscle radius. The equivalence of both parameters support the relevance of diffusion. A particular mechanism of receptor-controlled diffusion was implicated by the saturation of initial rates of uptake with increasing ouabain concentrations. Saturation of initial uptake indicates an inhomogeneity of receptor occupancy with ouabain-equilibrated receptors in the superficial areas of the preparation and free receptors in the muscle core. 2. For comparison [3H]-ouabain diffusion was evaluated in a non-cellular preparation i.e. glass fibre filters soaked with modified Krebs-Henseleit solution. Diffusion was approximately 3 orders of magnitude faster when compared with the papillary muscles. 3. The time course of the inotropic effect of ouabain on rested-state contractions dissociated from the tissue content of ouabain with an increased steroid concentration. This dissociation appears to be associated with the inhomogeneity of receptor occupancy, since equal amounts of the steroid correspond to different concentration profiles in the tissue when the bath concentration is changed. Functional coupling between different muscle areas may have modulated the influence of inhomogeneous receptor occupancy.