Effects of internal and external sodium on the sodium current-voltage relationship in the Squid giant axon

The early transient current-voltage relationship was measured in internally perfused voltage clamped squid giant axons with various concentrations of sodium on the two sides of the membrane. In the absence of sodium on either side there is an outward transient current which is blocked by tetrodotoxin and varies with internal potassium concentration. The current increases linearly with voltage for positive potentials. Adding sodium ions internally increases the slope of the current-voltage relationship. Adding sodium ions externally also increases the slope between +10 and +80 mV. Adding sodium to both sides produces the sum of the two effects. The current-voltage relationships were fit by straight lines between +10 and +80 mV. Plotting the extrapolated intercepts with the current axis against the differences in sodium concentrations gave a straight line, Io = -P (Co-Ci)F. P, the Fickian permeability, is about 10(-4) cm/sec. Plotting the slopes in three dimensions against the two sodium concentrations gave a plane g = go + (aNao + bNai)F. a is about 10(-6) cm/mV-sec and b about 3 x 10(-6) cm/mV-sec. Thus the current-voltage relationship for the sodium current is well described by I = -P(Co-Ci)F+ (aco + bci)FV for positive potentials. This is the linear sum of Fick's Law and Ohm's Law. P/(a + b) = 25 +/- 1 mV (N = 6) and did not vary with the absolute magnitude of the currents. Within experimental error this is equal to kT/e or RT/F. Increasing temperature increased P, a and b proportionately. Adding external calcium, lithium, or Tris selectively decreased P and a without changing b. In the absence of sodium, altering internal and external potassium while observing the early transient currents suggests this channel is more asymmetric in its response to potassium than to sodium.