Transient and persistent sodium currents in normal and denervated mammalian skeletal muscle

1. Transient and persistent tetrodotoxin-sensitive sodium currents were recorded in response to depolarizing voltage pulses in voltage clamped segments of rat extensor digitorum longus muscle fibres at 20-25 degrees C in a triple Vaseline gap. 2. Appreciable persistent sodium current but little or no transient current was seen in response to depolarizations of up to 15 mV from a holding potential of -100 mV. 3. The maximum amplitude of both transient and persistent sodium currents occurred with depolarizations to -40 mV: the average peak amplitude of the transient current in fibres with a holding potential of -90 mV was -0.22 +/- 0.03 mA/microF (mean +/- 1 S.E.M., seven fibres) and the average amplitude of the persistent current was -0.94 +/- 0.10 microA/microF (mean +/- 1 S.E.M., twelve fibres). With a holding potential of -100 mV, the average amplitudes of the transient and persistent currents were -0.46 +/- 0.10 mA/microF (four fibres) and -1.4 +/- 0.22 microA/microF (five fibres), respectively. 4. The average maximum persistent sodium conductance in seven fibres held at -90 mV was 0.13 +/- 0.0078 microS and the potential for half-maximum conductance was -53 +/- 0.74 mV (mean +/- 1 S.E.M.). 5. When the transient sodium current was completely inactivated with 100 ms conditioning depolarizations to potentials more positive than -50 to -60 mV, there was little inactivation of the persistent current. 6. In six denervated fibres, the average amplitudes of the transient and persistent sodium currents generated by pulses to -40 mV from a holding potential of -90 mV were -0.11 +/- 0.01 mA/microF and -0.88 +/- 0.12 microA/microF, respectively (mean +/- 1 S.E.M.). It was concluded that there was a decrease in transient current but not persistent current amplitude following denervation and that the persistent current in denervated fibres with an increased input resistance could give rise to the spontaneous action potentials responsible for fibrillation.