Reverse-engineered models reveal differential membrane properties of autonomic and cutaneous unmyelinated fibers.

Autor: Thio BJ; Department of Biomedical Engineering Duke University Durham, North Carolina, United States of America., Titus ND; Department of Biomedical Engineering Duke University Durham, North Carolina, United States of America., Pelot NA; Department of Biomedical Engineering Duke University Durham, North Carolina, United States of America., Grill WM; Department of Biomedical Engineering Duke University Durham, North Carolina, United States of America.; Duke University, Department of Electrical and Computer Engineering, Durham, North Carolina, United States of America.; Duke University School of Medicine, Department of Neurobiology, Durham, North Carolina, United States of America.; Duke University School of Medicine, Department of Neurosurgery, Durham, North Carolina, United States of America.
Jazyk: angličtina
Zdroj: PLoS computational biology [PLoS Comput Biol] 2024 Oct 07; Vol. 20 (10), pp. e1012475. Date of Electronic Publication: 2024 Oct 07 (Print Publication: 2024).
DOI: 10.1371/journal.pcbi.1012475
Abstrakt: Unmyelinated C-fibers constitute the vast majority of axons in peripheral nerves and play key roles in homeostasis and signaling pain. However, little is known about their ion channel expression, which controls their firing properties. Also, because of their small diameters (~ 1 μm), it has not been possible to characterize their membrane properties using voltage clamp. We developed a novel library of isoform-specific ion channel models to serve as the basis functions of our C-fiber models. We then developed a particle swarm optimization (PSO) framework that used the isoform-specific ion channel models to reverse engineer C-fiber membrane properties from measured autonomic and cutaneous C-fiber conduction responses. Our C-fiber models reproduced experimental conduction velocity, chronaxie, action potential duration, intracellular threshold, and paired pulse recovery cycle. The models also matched experimental activity-dependent slowing, a property not included in model optimization. We found that simple conduction responses, characterizing the action potential, were controlled by similar membrane properties in both the autonomic and cutaneous C-fiber models, but complicated conduction response, characterizing the afterpotenials, were controlled by differential membrane properties. The unmyelinated C-fiber models constitute important tools to study autonomic signaling, assess the mechanisms of pain, and design bioelectronic devices. Additionally, the novel reverse engineering approach can be applied to generate models of other neurons where voltage clamp data are not available.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Thio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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