Altered distribution of juxtaparanodal kv1.2 subunits mediates peripheral nerve hyperexcitability in type 2 diabetes mellitus.
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.
Department of Medical Genetics and Graduate Program in Neurosciences, University of Lausanne, CH-1005 Lausanne, Switzerland.
Jennifer
J
Zenker
Olivier
O
Poirot
Anne-Sophie
AS
de Preux Charles
Estelle
E
Arnaud
Jean-Jacques
JJ
Médard
Catherine
C
Lacroix
Thierry
T
Kuntzer
Roman
R
Chrast
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000367:Age Factors; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000473:pathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006801:Humans; D051663:Kv1.2 Potassium Channel / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D009431:Neural Conduction / Q000502:physiology; D010525:Peripheral Nerves / Q000378:metabolism* / Q000503:physiopathology*; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000473:pathology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D021122:Protein Subunits / Q000378:metabolism; D011901:Ranvier's Nodes / Q000378:metabolism*; D054411:Receptors, Leptin / Q000235:genetics; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D001786:Blood Glucose; D051663:Kv1.2 Potassium Channel; D026902:Potassium Channel Blockers; D021122:Protein Subunits; D054411:Receptors, Leptin; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin