MULTIPLE KINETIC COMPONENTS OF SODIUM-CHANNEL INACTIVATION IN RABBIT SCHWANN-CELLS

1. We have studied the kinetics of inactivation of sodium currents evoked in Schwann cells from neonatal and adult rabbits with patch-clamp recording techniques. The decay both of whole-cell currents and of ensemble currents obtained from outside-out patches was reasonably well-described by single exponential fits which gave values for the time constant, tau(h), similar to those found for such currents in nerve (about 0.5 ms at 0 mV). Although inclusion of an additional exponential component usually improved the fits to the decay of these currents, the relative amplitude of the slower component (time constant 3-6 ms) was always small. 2. The time course of recovery from steady-state inactivation clearly consisted of two exponential components. At -120 mV, recovery from steady-state inactivation at -50 mV consisted of a fast component with a time constant of 2.2 +/- 0.2 ms and a much slower component with a time constant of 1.2 +/- 0.2 s (n = 9). The relative amplitude of the slow component (expressed as a fraction of the sodium current when inactivation was removed completely) was 0.56 +/- 0.03. The corresponding amplitudes of the slow component when similar experiments were done from holding potentials of 0 and -70 mV were 0.80 +/- 0.04 and 0.36 +/- 0.03, respectively (n = 5 and 8). 3. The onset of steady-state inactivation also followed a bi-exponential time course. The time constant of the slower component was similar at each potential examined (0, -50 and -70 mV), being 6-7 s. The relative amplitude of the slow component of onset depended on membrane potential, and it was similar (at each potential examined) to the corresponding amplitude of the slow component of recovery. 4. The inclusion of 40 mm-iodate ions in the pipette solution slowed the decay of whole-cell sodium currents, as did the extracellular application of venom (10-mu-g ml-1) from the scorpion Leiurus quinquestriatus. Prolonged exposure of the cells to Leiurus venom appeared to increase the steady-state amount of slow inactivation. 5. Records of single-channel sodium currents tended to cluster into records which either did, or did not, contain openings. This apparently non-random behaviour depended on membrane potential, and on the frequency at which the test steps were repeated, in the way expected if it resulted from slow inactivation. 6. The results indicate that sodium channels in Schwann cells can exist in at least three different inactivated states and provide further evidence of the similarity between these sodium channels and sodium channels in excitable cells.