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

J Zenker, O Poirot, AS de Preux Charles… - Journal of …, 2012 - Soc Neuroscience
J Zenker, O Poirot, AS de Preux Charles, E Arnaud, JJ Médard, C Lacroix, T Kuntzer
Journal of Neuroscience, 2012Soc Neuroscience
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 Kv1-channels. In agreement with these data, we observed that the …
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 Kv1-channels. In agreement with these data, we observed that the diabetic condition led to a reduced presence of the Kv1.2-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.
Soc Neuroscience