Rate constants associated with changes in sodium conductance in axons perfused with sodium fluoride.

1. Membrane currents during step depolarizations were measured in axons which were perfused with 300 mM-NaF and placed in K-free artificial sea-water, -0.3-4 degrees C. The Na conductance was fitted by the modified Hodgkin-Huxley model, g(Na) = g(Na)m(3)(h(1) + h(2)). Changes in h(1) and h(2) were assumed to follow [Formula: see text] where x represents the inactive state.2. The rate constants and steady-state values for m were in agreement with the Hodgkin-Huxley equations except that the experimental relationship of m(infinity) (3) against V was shifted 10-15 mV in the negative direction. This discrepancy, which was not found in an experiment with choline sea-water, can be explained on the basis of a resistance in series with the membrane between the voltage measuring electrodes.3. At 0 degrees C the rate constants (in msec(-1)) associated with changes in h(1) and h(2) were fitted using the following equations: beta(h1) = 0.5/{exp [- (V + 32)/10] + D(1)exp (- V/V(1))}, alpha(h2) = pexp (V/V(2)), beta(h2) = pexp (V/V(2) - V/23.5) + pD(2), with the condition that at 0 mV, (alpha(h2) + beta(h2)) = p(D(2) + 2) = 0.55 msec(-1). The experiments gave average values D(1) = 3.6, V(1) = 240 mV, p = 0.08 msec(-1) and V(2) = 70 mV. The average value of g(Na) was 66 mmho/cm(2).4. At negative voltages where m(infinity) (3) against V is steep, the points for beta(h1) and alpha(h2)/beta(h2) from axons in Na sea-water were not fitted well by the above equations whereas data from an axon in choline sea-water were. These discrepancies can be explained on the basis of a series resistance.5. Measurements made at 16-17 degrees C indicated that g(Na) has a Q(10) of 1.6, tau(m) (-1) a Q(10) of 2.8 and beta(h1) a Q(10) of 3.5. The ratio alpha(h2)/beta(h2) was decreased relative to the value at 0 degrees C and could be fitted by using Q(10) = 0.6.6. Measurements made with 250 mM-NaF + 50 mM-KF inside gave rate constants which were very similar to those obtained with 300 mM-NaF. Perfusion with 300 mM-KF appeared to double the value of beta(h1), relative to that obtained with 300 mM-NaF, and to reduce alpha(h2)/beta(h2) by about half.7. The voltage dependence of alpha(h2) makes it likely that following depolarization recovery from the inactive state x occurs via x --> h(1) rather than x --> h(2) --> h(1).