Single-channel current/voltage relationships of two kinds of Na⁺ channel in vertebrate sensory neurons

Abstract

The electrical signals of nerve and muscle are fundamentally dependent on the voltage-gated Na⁺ channel, which is responsible for the rising phase of the action potential. At least two kinds of Na⁺ channel are expressed in the membrane of frog dorsal root ganglion (DRG) cells: Na⁺ channels with fast kinetics that are blocked by tetrodotoxin (TTX) at high affinity, and Na⁺ channels with slower kinetics that are insensitive to TTX. Recordings of single-channel currents from frog DRG cells, under conditions favoring Na⁺ as the charge carrier, reveal two distinct amplitudes of single-channel events. With 300 mM external Na⁺, single-channel events that can be measured in the presence of 1 μM TTX have a slope conductance 7.5 pS. In the absence of TTX, events with a slope conductance of 14.9 pS dominate. Ensemble averages of the smaller single-channel events display the slower kinetics characteristic of the macroscopic TTX-insensitive Na⁺ currents, and ensemble averages of the larger events display the faster kinetics characteristic of the TTX-sensitive currents. The results are consistent with the idea that the toxin-binding site is sufficiently close to the pore to influence ion permeation.