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1. We have recorded membrane potential, intracellular Na activity (aiNa) and force of contraction in sheep Purkinje fibres. Force and aiNa were recorded continuously and simultaneously during exposure to strophanthidin and its subsequent washing off. 2. Exposure to strophanthidin in concentrations of 1.5 X 10(-7), 5 X 10(-7) and 10(-5) M caused an increase in force of contraction which was temporally dissociated from the increase of aiNa. 3. There was hysteresis in the relationship between force and aiNa when the period of increasing force was compared to the period of decreasing force. When force increased on exposure to strophanthidin, the same aiNa was always associated with a higher force than when force was decreasing while washing off the drug. 4. For the same rise of aiNa higher doses of strophanthidin produced larger rises of force than lower doses. 5. When diphenylhydantoin was present in the bathing solution at concentrations of 10(-5) and 10(-4) M, the relation between force and aiNa with 10(-5) M-strophanthidin had a less steep slope, but still displayed hysteresis. 6. The relationship between force and aiNa during changes of the bathing K concentration also displayed a hysteresis, which was in the same direction as that found with strophanthidin. 7. These results are discussed in relation to proposed mechanisms of action of strophanthidin and more generally in relation to the factors linking force of contraction and aiNa. We conclude that in sheep Purkinje fibres the increase of force caused by strophanthidin is not solely due to an increase of aiNa, and that other interventions can also result in hysteresis between force and aiNa.

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