Upper and lower limb motor axons demonstrate differential excitability and accommodation to strong hyperpolarizing currents during induced hyperthermia


Length-dependent peripheral neuropathy typically involves the insidious onset of sensory loss in the lower limbs before later progressing proximally. Recent evidence proposes hyperpolarization-activated cyclic nucleotide-gated (HCN) channels as dysfunctional in rodent models of peripheral neuropathy, and therefore differential expression of HCN channels in the lower limbs was hypothesized as a pathophysiological mechanism accounting for the pattern of symptomatology within this study. We studied six healthy participants, using motor axon excitability including strong and long [-70% and -100% hyperpolarizing threshold electrotonus (TEh)] hyperpolarizing currents to preferably study HCN channel function from the median and tibial nerves from high (40%) and low (20%) threshold. This was recorded at normothermia (~32°C) and then repeated during hyperthermia (~40°C) as an artificial hyperpolarizing axon stress. Significant differences between recovery cycle, superexcitability, accommodation to small depolarizing currents, and alterations in late stages of the inward-rectifying currents of strongest (-70% and -100% TEh) currents were observed in the lower limbs during hyperthermia. We demonstrate differences in late IH current flow, which implies higher expression of HCN channel isoforms. The findings also indicate their potential inference in the symptomatology of length-dependent peripheral neuropathies and may be a unique target for minimizing symptomatology and pathogenesis in acquired disease. NEW & NOTEWORTHY This study demonstrates nerve excitability differences between the upper and lower limbs during hyperthermia, an experimentally induced axonal stress. The findings indicate that there is differential expression of slow hyperpolarization-activated cyclic nucleotide-gated (HCN) channel isoforms between the upper and lower limbs, which was demonstrated through strong, long hyperpolarizing currents during hyperthermia. Such mechanisms may underlie postural control but render the lower limbs susceptible to dysfunction in disease states.

Publication DOI: https://doi.org/10.1152/jn.00464.2018
Divisions: College of Health & Life Sciences > School of Psychology
College of Health & Life Sciences > Aston Institute of Health & Neurodevelopment (AIHN)
College of Health & Life Sciences
College of Health & Life Sciences > Clinical and Systems Neuroscience
Additional Information: Copyright © 2019, Journal of Neurophysiology
Uncontrolled Keywords: HCN channels,axon,hyperpolarization,hyperthermia,nerve excitability,peripheral neuropathy,Neuroscience(all),Physiology
Publication ISSN: 1522-1598
Last Modified: 20 May 2024 07:29
Date Deposited: 02 Apr 2019 14:00
Full Text Link:
Related URLs: https://www.phy ... 2/jn.00464.2018 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2019-06-01
Published Online Date: 2019-03-27
Accepted Date: 2019-03-26
Authors: Marmoy, Oliver Rajesh
Furlong, Paul Lawrence (ORCID Profile 0000-0002-9840-8586)
Moore, Christopher E G



Version: Accepted Version

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