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The Journal of Physiology - 2024 - Goodlich - Antagonism of 5‐HT2 receptors attenuates self‐sustained firing of human motor1.74 MB
Published VersionCC BY V4.0, Open Access
Journal article
Antagonism of 5-HT2 receptors attenuates self-sustained firing of human motor units
The Journal of Physiology, Vol.602(8), pp.1759-1774
2024
PMID: 38502567
Abstract
5-HT2 receptors on motoneurones play a critical role in facilitating persistent inward currents (PICs). Although facilitation of PICs can enhance self-sustained firing after periods of excitation, the relationship between 5-HT2 receptor activity and self-sustained firing in human motor units (MUs) has not been resolved. MU activity was assessed from the tibialis anterior of 10 healthy adults (24.9 +/- 2.8 years) during two contraction protocols. Both protocols featured steady-state isometric contractions with constant descending drive to the motoneurone pool. However, one protocol also included an additional phase of superimposed descending drive. Adding and then removing descending drive in the middle of steady-state contractions altered MU firing behaviour across the motor pool, where newly recruited units in the superimposed phase were unable to switch off (P = 0.0002), and units recruited prior to additional descending drive reduced their discharge rates (P < 0.0001, difference in estimated marginal means (triangle) = 2.24 pulses/s). The 5-HT2 receptor antagonist, cyproheptadine, was then administered to determine whether changes in MU firing were mediated by serotonergic mechanisms. 5-HT2 receptor antagonism caused reductions in MU discharge rate (P < 0.001, triangle = 1.65 pulses/s), recruitment threshold (P = 0.00112, triangle = 1.09% maximal voluntary contraction) and self-sustained firing duration (P < 0.0001, triangle = 1.77s) after the additional descending drive was removed in the middle of the steady-state contraction. These findings indicate that serotonergic neuromodulation plays a key role in facilitating discharge and self-sustained firing of human motoneurones, where adaptive changes in MU recruitment must occur to meet the demands of the contraction.
Details
- Title
- Antagonism of 5-HT2 receptors attenuates self-sustained firing of human motor units
- Authors
- Benjamin I. Goodlich (Corresponding Author) - Griffith UniversityGregory E. P. Pearcey - Memorial University of NewfoundlandAlessandro Del Vecchio - Friedrich-Alexander-Universität Erlangen-NürnbergSean A. Horan - Griffith UniversityJustin J. Kavanagh - Griffith University
- Publication details
- The Journal of Physiology, Vol.602(8), pp.1759-1774
- Publisher
- Wiley-Blackwell Publishing Ltd.
- Date published
- 2024
- DOI
- 10.1113/JP285867
- ISSN
- 1469-7793; 0022-3751
- PMID
- 38502567
- Copyright note
- © 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Data Availability
- The data that support the findings of this study are available on request from the corresponding author.
- Grant note
- European Research Council (ERC). Grant Number: 101118089
- Organisation Unit
- School of Health - Sports & Exercise Science
- Language
- English
- Record Identifier
- 991081292402621
- Output Type
- Journal article
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- Domestic collaboration
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- Web Of Science research areas
- Neurosciences
- Physiology