Effect of prolonged depolarizations on twitch tension and intracellular sodium activity in sheep cardiac Purkinje fibres.

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Abstract
1. Twitch tension and intracellular Na+ activity .**GRAPHIC**. were measured in voltage-clamped sheep cardiac Purkinge fibres. .**GRAPHIC**. was measured using Na+-sensitive micro-electrodes filled with the liquid ion exchange resin. ETH 227. The stimulus for contraction was a constant 200 ms depolarizing pulse to 0 mV from a holding potential of -80 mV delivered at 0.25 Hz. Prolonged test pulses for 1.8 s (post-pulses) were applied to the end of the stimulus pulse. The effects of post-pulses on twich tension and .**GRAPHIC**. were examined. 2. Post-pulses in the range of -40 mV produced twitch tension below control force produced without post-pulse. Progressively more positive post-pulses to levels above 0 mV profoundly increased twitch tension, with a greater than 400% rise in tension at +50 to +60 mV compared to control tension. .**GRAPHIC**. declined at positive post-pulse potentials by more than 2 mM at +30 to +40 mV. 3. Tetrodotoxin (100 .mu.M) did not affect the post-pulse voltage-tension or .**GRAPHIC**. relation. Ca2+ channel modulation with nitrendipine (1 .mu.m) similarly did not alter the post-pulse voltage-tension relation. 4. Removal of extracellular Na+ eliminated the nadir in tension at post-pulses to -40 mV and the augmentation of tension at post-pulses above 0 mV. 5. We interpret these findings evidence of voltage-sensitive Na-Ca exchange promoting net Ca2+ influx and net Na+ efflux during positive post-pulses. The unusual shape of the post-pulse voltage-tension relation curve can be accounted for by a charged-carrier model of electrogenic Na-Ca exchange. The inverse relation between .**GRAPHIC**. and twitch tension probably reflects the combined effects of reduced .**GRAPHIC**. leak and changes in Na+ and Ca2+ flux voltage-sensitive Na-Ca exchange.