Differential sensitivity of fast and slow fibers in mammalian nerve. II. Margin of safety for nerve transmission.

In a previous study it was found that concentrations of local anesthetics required to block large, fast-conducting nerve fibers were lower than those required to block small, slow-conducting fibers. The present study was instituted to evaluate the margin of safety for transmission in large versus small nerve fibers, the margin of safety being defined as the ratio between the magnitude of the action potential and the magnitude of the critical membrane potential. The effect of reducing the sodium-activating current, which reduces the magnitude of the action potential by sodium deficient solutions and tetrodotoxin application to the desheathed rabbit vagus nerve trunk (in vitro), was examined. Anode block (another method of reducing sodium current) is also discussed. In all instances, the margin of safety for transmission was greater in small, slow fibers than in large, fast fibers. The variations seen in nerve response to tetrodotoxin application are explained by the presence of nerve fiber diffusion barriers; the large fibers show more diffusion protection than the small fibers. Onset, duration, and intensity of differential nerve blockade by drugs reflect a balance between diffusion barriers and axon membrane sensitivity.