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

Abstract

1. The intracellular Na activity (a(Na) (i)) 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 x 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 x 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 x 10(-3)M) also reduced the rate of rise of intracellular Na produced by the removal of external K (K(o)), and prevented the large depolarization associated with the absence of K(o).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.