Conductance of the sodium channel in myelinated nerve fibres with modified sodium inactivation.

Abstract

Na+ current fluctuations in [frog] nodes of Ranvier were measured under voltage clamp conditions and analyzed in terms of power spectral density calculated for frequencies between 30 Hz-5 kHz. External (10-5 g/ml) Leiurus [quinquestriatus] scorpion venom or Anemonia [sulcata] Toxin II (3 .times. 10-5 g/ml) or internal 20 nM iodate were applied to remove or slow down inactivation in part of the Na+ channels. The treatment increased the steady-state Na+ current during the noise measurement 1-8 fold over that in normal fibers. Noise spectra were interpreted as the sum of 1/f noise and noise SNa(f) due to all-or-none, open-close transitions of single Na+ channels. The drug effects on the inactivation could be accounted for either by assuming 2 populations of channels, one with and one without inactivation, or by postulating a single population with modified inactivation characteristics. Except for an increase in amplitude, the fluctuation spectra SNa(f) were similar to the ones in normal nodes. Again, the time constants .tau.m obtained from the fit of the spectra agreed within a factor of 2 with the values of .tau.m found in the macroscopic Na+ currents. From the fluctuation spectra, single Na+ channel conductances .gamma. of 5.4 .+-. 0.4 pS [Siemen] (iodate), 6.7 .+-. 0.5 pS (Leiurus) and 7.0 .+-. 0.6 pS (Anemonia) were calculated. The value of .gamma. was not significantly voltage dependent. Inactivation of Na+ channels can apparently be modified with at most small effects on the microscopic properties of the activation process and on the conductance of the open channel. They suggest that the h mechanism normally produces all-or-none, open-close changes of conductance.