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Department of Physiology, State University of New York, Brooklyn 11203.

1. The effects of different concentrations of strophanthidin on intracellular sodium activity (aiNa), membrane potential and contractile force have been studied in cardiac sheep Purkinje fibres under conditions (overdrive) that stimulate Na+-K+ pump activity. 2. In fibres driven at 1 Hz, a 5 min overdrive at 2 Hz in the steady state increased force by +74.2%, aiNa by +10.9% and the maximum diastolic potential (Emax) by 3.32 +/- 0.52 mV. 3. During the recovery from overdrive (the fibres being driven again at 1 Hz), both contractile force and aiNa transiently undershot the control value by -10.5 and -3.7%, respectively. When the fibres were quiescent during the recovery from overdrive, no aiNa undershoot was present. 4. During overdrive, force and aiNa were closely correlated when plotted either on linear (correlation coefficient, R = 0.98) or logarithmic (R = 0.98) co-ordinates. 5. A low concentration of strophanthidin (0.01 microM) decreased force (-31.7%) and aiNa (-7.2%): overdrive increased force and Emax more and aiNa less than in the absence of strophanthidin. During the recovery, the undershoot in force (-12.9%) and aiNa (-5.4%) was larger and longer than in the absence of strophanthidin. 6. An intermediate concentration of strophanthidin (0.05 microM) increased force (+43.5%) and aiNa (+6.4%): overdrive increased force and aiNa as usual, but during the recovery the force remained above the value prior to overdrive and there was no aiNa undershoot. 7. A high concentration of strophanthidin (0.1 microM) increased force (+91.4%) and aiNa (+11.7%): overdrive further increased force and aiNa more than in control but there was no increase in Emax. During the recovery, both force and aiNa remained well above the values prior to overdrive. 8. Force and aiNa were closely correlated whether aiNa decreased in 0.01 microM-strophanthidin (R = 0.99 both on linear and logarithmic co-ordinates) or increased in 0.05-microM- (R = 1.00 on both co-ordinates) and in 0.1 microM- (R = 0.98 and 0.99, respectively) strophanthidin. The two parameters were well correlated also during overdrive in the three strophanthidin solutions. However, the slope of the relation was less steep in the low- than in the higher-strophanthidin solutions. 9. For a 1 mM change in aiNa, force decreased less in the low- than it increased in the intermediate-strophanthidin solution. Also, in low-strophanthidin solution, at the end of overdrive the aNao/aNai ratio was similar to that in Tyrode solution but force was well above control (+73.2%).(ABSTRACT TRUNCATED AT 400 WORDS)