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Title: A study of sodium channels in normal sensory neurons and in those affected by autoimmune inflammatory demyelinating disease
Author: Farmer, Clare Elizabeth
ISNI:       0000 0004 0109 1864
Awarding Body: King's College London (University of London)
Current Institution: King's College London (University of London)
Date of Award: 2008
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Experimental autoimmune neuritis (EAN) is an inflammatory demyelinating peripheral neuropathy that serves as an animal model for the human disease Guillain-Barre syndrome (GBS). Conduction deficits and aberrant electrical behaviour in neurons can contribute to the production of neurological signs or symptoms in both EAN and GBS, and changes in the expression or function of voltage-gated sodium channels (VGSCs) may be involved in this neuronal dysfunction. The work described in this thesis is aimed at studying peripheral sensory neurons in both normal rats, and rats with EAN, using electrophysiological methods designed to reveal changes in VGSC function. Initial work characterised the effects of three VGSC blocking agents on conduction along sensory axons from naive animals using an in vitro grease-gap recording technique. This technique was then used to study the pharmacology of two of these agents on sensory nerve conduction in nerves taken from animals with EAN. In addition, a detailed study of voltage-gated sodium currents in sensory neurons in EAN was performed using the whole-cell voltage clamp technique. Primary cultures of lumbar DRG neurons were used, and cells were divided into two groups, those expressing purely tetrodotoxin-sensitive (TTXS) currents and those expressing mixed sodium currents from which tetrodotoxin-resistant (TTXR) currents could be isolated using tetrodotoxin (TTX). Activation and inactivation characteristics of the three populations of currents were compared between EAN and naive groups. The final part of the study focused on the effects of pre-activated macrophages on sodium currents in EAN. The same three types of sodium currents were examined by voltage clamp in DRG neurons from animals with EAN following a 20-28 hour co-culture with the macrophages, and compared with those in neurons cultured without macrophages.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available