The anticonvulsant retigabine suppresses neuronal Kv2-mediated currents

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

Jeroen I Stas, Elke Bocksteins, Camilla S Jensen, Nicole Schmitt, Dirk J Snyders

Enhancement of neuronal M-currents, generated through KV7.2-KV7.5 channels, has gained much interest for its potential in developing treatments for hyperexcitability-related disorders such as epilepsy. Retigabine, a KV7 channel opener, has proven to be an effective anticonvulsant and has recently also gained attention due to its neuroprotective properties. In the present study, we found that the auxiliary KCNE2 subunit reduced the KV7.2-KV7.3 retigabine sensitivity approximately 5-fold. In addition, using both mammalian expression systems and cultured hippocampal neurons we determined that low μM retigabine concentrations had 'off-target' effects on KV2.1 channels which have recently been implicated in apoptosis. Clinical retigabine concentrations (0.3-3 μM) inhibited KV2.1 channel function upon prolonged exposure. The suppression of the KV2.1 conductance was only partially reversible. Our results identified KV2.1 as a new molecular target for retigabine, thus giving a potential explanation for retigabine's neuroprotective properties.

OriginalsprogEngelsk
Artikelnummer35080
TidsskriftScientific Reports
Vol/bind6
Antal sider12
ISSN2045-2322
DOI
StatusUdgivet - 13 okt. 2016

Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk


Ingen data tilgængelig

ID: 167356343