Altered distribution of juxtaparanodal kv1.2 subunits mediates peripheral nerve hyperexcitability in type 2 diabetes mellitus.

Details

Ressource 1Download: BIB_2F08BC0A9846.P001.pdf (1211.29 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_2F08BC0A9846
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Altered distribution of juxtaparanodal kv1.2 subunits mediates peripheral nerve hyperexcitability in type 2 diabetes mellitus.
Journal
Journal of Neuroscience
Author(s)
Zenker J., Poirot O., de Preux Charles A.S., Arnaud E., Médard J.J., Lacroix C., Kuntzer T., Chrast R.
ISSN
1529-2401 (Electronic)
ISSN-L
0270-6474
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
32
Number
22
Pages
7493-7498
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Peripheral nerve hyperexcitability (PNH) is one of the distal peripheral neuropathy phenotypes often present in patients affected by type 2 diabetes mellitus (T2DM). Through in vivo and ex vivo electrophysiological recordings in db/db mice, a model of T2DM, we observed that, in addition to reduced nerve conduction velocity, db/db mice also develop PNH. By using pharmacological inhibitors, we demonstrated that the PNH is mediated by the decreased activity of K(v)1-channels. In agreement with these data, we observed that the diabetic condition led to a reduced presence of the K(v)1.2-subunits in juxtaparanodal regions of peripheral nerves in db/db mice and in nerve biopsies from T2DM patients. Together, these observations indicate that the T2DM condition leads to potassium channel-mediated PNH, thus identifying them as a potential drug target to treat some of the DPN related symptoms.
Keywords
Action Potentials/drug effects, Action Potentials/genetics, Age Factors, Animals, Blood Glucose/metabolism, Body Weight/drug effects, Body Weight/genetics, Diabetes Mellitus, Type 2/complications, Diabetes Mellitus, Type 2/pathology, Disease Models, Animal, Electric Stimulation, Humans, Kv1.2 Potassium Channel/metabolism, Male, Mice, Mice, Mutant Strains, Mutation/genetics, Neural Conduction/physiology, Peripheral Nerves/metabolism, Peripheral Nerves/physiopathology, Peripheral Nervous System Diseases/etiology, Peripheral Nervous System Diseases/pathology, Potassium Channel Blockers/pharmacology, Protein Subunits/metabolism, Ranvier's Nodes/metabolism, Receptors, Leptin/genetics, Sodium Channel Blockers/pharmacology, Sodium Channels/metabolism, Tetrodotoxin/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
26/10/2012 11:02
Last modification date
20/08/2019 13:13
Usage data