TY - JOUR
T1 - Aging-associated changes in motor axon voltage-gated Na+ channel function in mice
AU - Moldovan, Mihai
AU - Rosberg, Mette Romer
AU - Alvarez Herrero, Susana
AU - Klein, Dennis
AU - Martini, Rudolf
AU - Krarup, Christian
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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 Nav1.8 voltage-gated Na+ channels on motor axons aggravating the functional impairment. The aim of the present study was to investigate the effect of regular aging on motor axon function with particular emphasis on Nav1.8. 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 mice were depolarized. An increased Nav1.8 isoform expression was found by immunohistochemistry. The depolarizing excitability features were absent in Nav1.8 null mice, and they were counteracted in WT mice by a Nav1.8 blocker. Our data suggest that alteration in voltage-gated Na+ channel isoform expression contributes to changes in motor axon function during aging.
AB - 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 Nav1.8 voltage-gated Na+ channels on motor axons aggravating the functional impairment. The aim of the present study was to investigate the effect of regular aging on motor axon function with particular emphasis on Nav1.8. 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 mice were depolarized. An increased Nav1.8 isoform expression was found by immunohistochemistry. The depolarizing excitability features were absent in Nav1.8 null mice, and they were counteracted in WT mice by a Nav1.8 blocker. Our data suggest that alteration in voltage-gated Na+ channel isoform expression contributes to changes in motor axon function during aging.
KW - Aging
KW - Excitability
KW - Internode
KW - Nerve activity
KW - Node of Ranvier
KW - Voltage-gated sodium channels
U2 - 10.1016/j.neurobiolaging.2015.12.005
DO - 10.1016/j.neurobiolaging.2015.12.005
M3 - Journal article
C2 - 26923409
AN - SCOPUS:84959454763
SN - 0197-4580
VL - 39
SP - 128
EP - 139
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -