Preferential conduction block of myelinated axons by nitric oxide
While extracellular signals recorded from myelinated fibers are in the range of 0.5 to 5 mV and are readily detected, action potentials from unmyelinated fibers in adult nerves are typically only 0.01 to 0.05 mV and must be extracted from background noise. This can be done with appropriate low‐noise amplifiers and signal averaging. While we recorded from a variety of adult tissues, we also examined developing nerves, in which the signals from unmyelinated (i.e., premyelinated) fibers are more robust. We applied NO through the use of a chemical donor, diethylamine NONOate (DEA NONOate). This compound was particularly useful for these experiments in part because a wide variety of controls and calculations have been done with it. Its half‐life, releasing NO, is 16 min at 22 °C to 25 °C and 2 min at 37 °C, rates which we verified through use of the Griess reagent (Green et al., 1982; Shrager et al., 1998). Correspondingly, its effects were minimal at 25 °C and only blocked when the temperature was raised to 37 °C, showing that the undissociated compound was without effect. Further, solutions were ineffective if allowed to fully dissociate into diethylamine and NO before applying to nerves (Shrager et al., 1998). (The half‐life of NO in aqueous solutions is ∼30 sec [Palmer et al., 1987].) Finally, solving the diffusion equation for a cylinder, and including the half‐life of NO in tissue (∼4 sec), we showed that at concentrations of the order used, DEA NONOate at 37 °C produces levels of NO in nerves that are similar to those that activated macrophages would produce in an inflammatory lesion (∼1 μM) (Shrager et al., 1998). Here we show that in both the central nervous system (CNS) and peripheral nervous system (PNS), in regions that contain both myelinated and unmyelinated axons, conduction in myelinated fibers is preferentially blocked by NO.