Aging-associated changes in motor axon voltage-gated Na+ channel function in mice

Abstract Accumulating myelin abnormalities and conduction slowing occur in peripheral nerves during aging. In mice deficient of myelin protein P0 severe peripheral nervous system myelin damage is associated with ectopic expression of Nav 1.8 voltage-gated Na+ channels (VGSC) on motor axons aggravating the functional impairment. The aim of the current study was to investigate the effect of regular aging on motor axon function with particular emphasis on Nav 1.8. We compared tibial nerve conduction and excitability measures by threshold-tracking in 12 months (mature) and 20 months (aged) wild-type (WT) mice. With aging, deviations during threshold electrotonus were attenuated and the resting current-threshold slope and early refractoriness were increased. Modeling indicated that, in addition to changes in passive membrane properties, motor fibers in aged WT were depolarized. An increased Nav 1.8 isoform expression was found by immunohistochemistry. The depolarizing excitability features were absent in Nav 1.8 null mice, and they were counteracted in WT by a Nav 1.8 blocker. Our data suggest that alteration in VGSC isoform expression contributes to changes in motor axon function during aging.