Probing functional properties of nociceptive axons using a microfluidic culture system.

Pathological changes in axonal function are integral features of many neurological disorders, yet our knowledge of the molecular basis of axonal dysfunction remains limited. Microfluidic chambers (MFCs) can provide unique insight into the axonal compartment independent of the soma. Here we demonstra...

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Autores principales:	Christoforos Tsantoulas, Clare Farmer, Patricia Machado, Katsuhiro Baba, Stephen B McMahon, Ramin Raouf
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d54372b54f884250a3d7710e915f2996
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spelling	oai:doaj.org-article:d54372b54f884250a3d7710e915f29962021-11-18T08:45:27ZProbing functional properties of nociceptive axons using a microfluidic culture system.1932-620310.1371/journal.pone.0080722https://doaj.org/article/d54372b54f884250a3d7710e915f29962013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24278311/?tool=EBIhttps://doaj.org/toc/1932-6203Pathological changes in axonal function are integral features of many neurological disorders, yet our knowledge of the molecular basis of axonal dysfunction remains limited. Microfluidic chambers (MFCs) can provide unique insight into the axonal compartment independent of the soma. Here we demonstrate how an MFC based cell culture system can be readily adapted for the study of axonal function in vitro. We illustrate the ease and versatility to assay electrogenesis and conduction of action potentials (APs) in naïve, damaged or sensitized DRG axons using calcium imaging at the soma for pharmacological screening or patch-clamp electrophysiology for detailed biophysical characterisation. To demonstrate the adaptability of the system, we report by way of example functional changes in nociceptor axons following sensitization by neurotrophins and axotomy in vitro. We show that NGF can locally sensitize axonal responses to capsaicin, independent of the soma. Axotomizing neurons in MFC results in a significant increase in the proportion of neurons that respond to axonal stimulation, and interestingly leads to accumulation of Nav1.8 channels in regenerating axons. Axotomy also augmented AP amplitude following axotomy and altered activation thresholds in a subpopulation of regenerating axons. We further show how the system can readily be used to study modulation of axonal function by non-neuronal cells such as keratinocytes. Hence we describe a novel in vitro platform for the study of axonal function and a surrogate model for nerve injury and sensitization.Christoforos TsantoulasClare FarmerPatricia MachadoKatsuhiro BabaStephen B McMahonRamin RaoufPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e80722 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christoforos Tsantoulas Clare Farmer Patricia Machado Katsuhiro Baba Stephen B McMahon Ramin Raouf Probing functional properties of nociceptive axons using a microfluidic culture system.
description	Pathological changes in axonal function are integral features of many neurological disorders, yet our knowledge of the molecular basis of axonal dysfunction remains limited. Microfluidic chambers (MFCs) can provide unique insight into the axonal compartment independent of the soma. Here we demonstrate how an MFC based cell culture system can be readily adapted for the study of axonal function in vitro. We illustrate the ease and versatility to assay electrogenesis and conduction of action potentials (APs) in naïve, damaged or sensitized DRG axons using calcium imaging at the soma for pharmacological screening or patch-clamp electrophysiology for detailed biophysical characterisation. To demonstrate the adaptability of the system, we report by way of example functional changes in nociceptor axons following sensitization by neurotrophins and axotomy in vitro. We show that NGF can locally sensitize axonal responses to capsaicin, independent of the soma. Axotomizing neurons in MFC results in a significant increase in the proportion of neurons that respond to axonal stimulation, and interestingly leads to accumulation of Nav1.8 channels in regenerating axons. Axotomy also augmented AP amplitude following axotomy and altered activation thresholds in a subpopulation of regenerating axons. We further show how the system can readily be used to study modulation of axonal function by non-neuronal cells such as keratinocytes. Hence we describe a novel in vitro platform for the study of axonal function and a surrogate model for nerve injury and sensitization.
format	article
author	Christoforos Tsantoulas Clare Farmer Patricia Machado Katsuhiro Baba Stephen B McMahon Ramin Raouf
author_facet	Christoforos Tsantoulas Clare Farmer Patricia Machado Katsuhiro Baba Stephen B McMahon Ramin Raouf
author_sort	Christoforos Tsantoulas
title	Probing functional properties of nociceptive axons using a microfluidic culture system.
title_short	Probing functional properties of nociceptive axons using a microfluidic culture system.
title_full	Probing functional properties of nociceptive axons using a microfluidic culture system.
title_fullStr	Probing functional properties of nociceptive axons using a microfluidic culture system.
title_full_unstemmed	Probing functional properties of nociceptive axons using a microfluidic culture system.
title_sort	probing functional properties of nociceptive axons using a microfluidic culture system.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/d54372b54f884250a3d7710e915f2996
work_keys_str_mv	AT christoforostsantoulas probingfunctionalpropertiesofnociceptiveaxonsusingamicrofluidicculturesystem AT clarefarmer probingfunctionalpropertiesofnociceptiveaxonsusingamicrofluidicculturesystem AT patriciamachado probingfunctionalpropertiesofnociceptiveaxonsusingamicrofluidicculturesystem AT katsuhirobaba probingfunctionalpropertiesofnociceptiveaxonsusingamicrofluidicculturesystem AT stephenbmcmahon probingfunctionalpropertiesofnociceptiveaxonsusingamicrofluidicculturesystem AT raminraouf probingfunctionalpropertiesofnociceptiveaxonsusingamicrofluidicculturesystem
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Probing functional properties of nociceptive axons using a microfluidic culture system.

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