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Effects of stimulation and diphenylhydantoin on the intracellular sodium activity in Purkinje fibres of sheep heart.

The effects of stimulus frequency on the intracellular Na+ activity (aiNa) of Purkinje fibres from sheep hearts have been investigated using ion‐sensitive micro‐electrodes. aiNa increased by approximately 44% at 3 Hz and approximately 6.5% at 0.2 Hz. The size of the increase was very variable between preparations and did not appear to be related to the initial level of aiNa before stimulation. During stimulation, the rise of aiNa was exponential and gave a new steady‐state level within about 15 min. The time constant of this rise was independent of the frequency of stimulation. The recovery of aiNa following a period of stimulation also appeared to be exponential but the time constant was dependent upon the extent to which aiNa had been raised during stimulation, with shorter time constants following larger rises. The effects of stimulation on aiNa were compared to inhibition of the Na+‐K+ pump using high concentrations of cardioactive steroids. The influence of diphenylhydantoin (DPH) on the Na+ permeability of the cell membrane was assessed by measuring the rate of rise of aiNa following Na+‐K+‐pump inhibition. DPH decreased the rate of rise of aiNa by approximately 37% at concentration of 10(‐4) M. The decrease of Na+ permeability produced by DPH is probably responsible for the observed reduction of aiNa in quiescent preparations. DPH also produced substantial decreases of aiNa in stimulated preparations. These results are discussed in relation to its known anti‐arrhythmic effects.