The intracellular sodium activity of sheep heart Purkinje fibres: effects of local anaesthetics and tetrodotoxin

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Abstract
1. The intracellular Na activity (aNai) of quiescent sheep heart Purkinje fibres has been measured using Na+‐sensitive glass micro‐electrodes. The effects of local anaesthetics (procaine and lidocaine) and tetrodotoxin (TTX) have been investigated.2. Local anaesthetics reduced the steady‐state level of the intracellular Na activity in a dose‐dependent manner. The highest concentrations used (10−2 M) reduced the intracellular Na activity by about 25%.3. TTX decreased the steady‐state level of the intracellular Na activity. At a concentration of 10−6 g/ml. (3·13 × 10−6 M), TTX produced a decrease in intracellular Na activity of approximately 10%.4. The initial rate of rise of the intracellular Na activity upon addition of the cardioactive steroid strophanthidin (10−5 M) was used to estimate the net passive Na influx.5. Procaine (5 × 10−4 M) caused a 50% reduction of this rate of rise of the intracellular Na activity. The highest concentration of procaine used (10−2 M) decreased the rate of rise by approximately 80%.6. Procaine (5 × 10−3 M) also reduced the rate of rise of intracellular Na produced by the removal of external K (Ko), and prevented the large depolarization associated with the absence of Ko.7. TTX also produced a decrease in the rate of rise of the intracellular Na activity that occurs upon addition of strophanthidin. A maximum effect was produced in our experiments at a TTX concentration of 10−6 g/ml. At this concentration the rate of rise of intracellular Na activity was reduced by approximately 40% at a membrane potential of ‐70 mV.8. We conclude from our experiments that the effects of local anaesthetics and TTX on the intracellular Na activity are brought about by a reduction of the Na permeability of the cell membrane, and that at the normal resting potential, Na entry through TTX‐sensitive channels contributes greatly to the total net Na influx.