title: Axonal excitability in X-linked dominant Charcot Marie Tooth disease.
abstract: OBJECTIVE
  We investigated peripheral nerve function in X-linked Charcot-Marie-Tooth disease type 1 (CMTX1), and considered the functional consequences of mutant connexin-32.
  
  
  METHODS
  Twelve subjects (9 female, 3 male) were assessed clinically, by nerve conduction and excitability studies. A model of myelinated axon was used to clarify the contributing changes.
  
  
  RESULTS
  All subjects had abnormal nerve conduction. Excitability studies on median nerve axons showed greater threshold changes to hyperpolarising currents, with "fanning out" in threshold electrotonus, and modest changes in the recovery cycle. Modelling suggested shortening of internodal length, increase in nodal fast potassium currents, shift of the voltage activation hyperpolarisation-activated cyclic-nucleotide-gated channels, and axonal hyperpolarisation. Plotting threshold versus extent of hyperpolarising threshold change in threshold electrotonus distinguished the CMTX1 patients from other chronic demyelinating neuropathies reported in the literature except hereditary neuropathy with pressure palsies (HNPP).
  
  
  CONCLUSIONS
  Some measures of axonal excitability are similar in CMTX1 and HNPP (though not the recovery cycle), but they differ from those in other chronic demyelinating neuropathies. The findings in CMTX1 are consistent with known pathology, but are not correlated to neuropathy severity.
  
  
  CONCLUSIONS
  The findings in CMTX1 could be largely the result of morphological alterations, rather than plasticity in channel expression or distribution.
authors.affiliation: Department of Neurology and Clinical Neurophysiology, Royal North Shore Hospital, NSW, Australia; The University of Sydney, NSW, Australia.
authors.forename: Christina
authors.initials: C
authors.lastname: Liang
authors.affiliation: Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, NSW, Australia; The University of Sydney, NSW, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Howells
authors.affiliation: ANZAC Research Institute, Concord Repatriation Hospital, NSW, Australia; The University of Sydney, NSW, Australia.
authors.forename: Marina
authors.initials: M
authors.lastname: Kennerson
authors.affiliation: ANZAC Research Institute, Concord Repatriation Hospital, NSW, Australia; The University of Sydney, NSW, Australia.
authors.forename: Garth A
authors.initials: GA
authors.lastname: Nicholson
authors.affiliation: Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, NSW, Australia; The University of Sydney, NSW, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Burke
authors.affiliation: Department of Neurology and Clinical Neurophysiology, Royal North Shore Hospital, NSW, Australia; Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, NSW, Australia; The University of Sydney, NSW, Australia. Electronic address: karl.ng@sydney.edu.au.
authors.forename: Karl
authors.initials: K
authors.lastname: Ng
mesh_terms: D000328:Adult; D000368:Aged; D001369:Axons / Q000502:physiology*; D002607:Charcot-Marie-Tooth Disease / Q000503:physiopathology*; D017630:Connexins / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000503:physiopathology*; D008875:Middle Aged; D008959:Models, Neurological; D009154:Mutation; D010525:Peripheral Nerves / Q000503:physiopathology*; D055815:Young Adult; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D000097002:Gap Junction beta-1 Protein
keywords: CMTX; Connexin-32; Demyelination; GJB1; Nerve excitability