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

Mihai Moldovan; Mette Romer Rosberg; Susana Alvarez Herrero; Dennis Klein; Rudolf Martini; Christian Krarup

doi:10.1016/j.neurobiolaging.2015.12.005

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

Mihai Moldovan, Mette Romer Rosberg, Susana Alvarez Herrero, Dennis Klein, Rudolf Martini, Christian Krarup^*

^*Corresponding author for this work

12 Citations (Scopus)

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 Na_v1.8 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 Na_v1.8. 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 Na_v1.8 isoform expression was found by immunohistochemistry. The depolarizing excitability features were absent in Na_v1.8 null mice, and they were counteracted in WT mice by a Na_v1.8 blocker. Our data suggest that alteration in voltage-gated Na⁺ channel isoform expression contributes to changes in motor axon function during aging.

Original language	English
Journal	Neurobiology of Aging
Volume	39
Pages (from-to)	128-139
Number of pages	12
ISSN	0197-4580
DOIs	https://doi.org/10.1016/j.neurobiolaging.2015.12.005
Publication status	Published - 1 Mar 2016

Keywords

Aging
Excitability
Internode
Nerve activity
Node of Ranvier
Voltage-gated sodium channels

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10.1016/j.neurobiolaging.2015.12.005

Cite this

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title = "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 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.",

keywords = "Aging, Excitability, Internode, Nerve activity, Node of Ranvier, Voltage-gated sodium channels",

author = "Mihai Moldovan and Rosberg, {Mette Romer} and {Alvarez Herrero}, Susana and Dennis Klein and Rudolf Martini and Christian Krarup",

year = "2016",

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doi = "10.1016/j.neurobiolaging.2015.12.005",

language = "English",

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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 -