Undershoots of intracellular sodium and the strength of contraction when the sodium-potassium pump of isolated sheep Purkinje fibres is reactivated by potassium.

We have recorded changes of membrane current, intracellular Na+ activity (aiNa), intracellular pH (pHi) and the strength of contraction in voltage-clamped sheep Purkinje fibres during and after inhibition of the Na(+)-K+ pump. The pump was inhibited by the removal of K+ from the bathing solution and this resulted in a rise in aiNa. On return of K+ to the bathing medium to reactivate the Na(+)-K+ pump there was a fall of aiNa to below its control value after which aiNa slowly returned to its control value over the next 20 min. This 'undershoot' of aiNa was seen in 69% of contracting fibres and 78% of quiescent fibres, and the mean (+/- S.D.) values of the undershoot in contracting and quiescent fibres were 0.66 +/- 0.15 and 0.9 +/- 0.35 mM, respectively. The undershoot of aiNa was observed regardless of whether the Na(+)-K+ pump was reactivated with Rb+ or K+. It was not voltage dependent over the potential range studied (-95 to -45 mV) and was not accompanied by a change of intracellular pH. The undershoot of aiNa could be the result of a long-lasting increase in Na+ efflux or a long-lasting decrease in Na+ influx. Zero [K+]o resulted in the loss of one Na+ current, the pacemaker current i(f), but when K+ was returned to the bathing medium i(f) recovered rapidly and is therefore unlikely to be responsible for the long-lasting undershoot of aiNa. This conclusion was confirmed by the use of Cs+: although Cs+ blocked i(f), it did not block the undershoot of aiNa. The undershoot of aiNa was accompanied by (and, via Na(+)-Ca2+ exchange, was presumably the cause of) an undershoot of the force of contraction. Undershoots are not only seen after reactivation of the Na(+)-K+ pump: in a variety of different preparations, similar undershoots in aiNa and twitch force have been reported after a decrease in the frequency of stimulation. The undershoot of aiNa may be the result of novel feedback mechanism for the control of aiNa: the control of Na+ influx by aiNa.