The anticonvulsant retigabine suppresses neuronal Kv2-mediated currents

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The anticonvulsant retigabine suppresses neuronal Kv2-mediated currents. / Stas, Jeroen I; Bocksteins, Elke; Jensen, Camilla S; Schmitt, Nicole; Snyders, Dirk J.

In: Scientific Reports, Vol. 6, 35080, 13.10.2016.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Stas, JI, Bocksteins, E, Jensen, CS, Schmitt, N & Snyders, DJ 2016, 'The anticonvulsant retigabine suppresses neuronal Kv2-mediated currents', Scientific Reports, vol. 6, 35080. https://doi.org/10.1038/srep35080

APA

Stas, J. I., Bocksteins, E., Jensen, C. S., Schmitt, N., & Snyders, D. J. (2016). The anticonvulsant retigabine suppresses neuronal Kv2-mediated currents. Scientific Reports, 6, [35080]. https://doi.org/10.1038/srep35080

Vancouver

Stas JI, Bocksteins E, Jensen CS, Schmitt N, Snyders DJ. The anticonvulsant retigabine suppresses neuronal Kv2-mediated currents. Scientific Reports. 2016 Oct 13;6. 35080. https://doi.org/10.1038/srep35080

Author

Stas, Jeroen I ; Bocksteins, Elke ; Jensen, Camilla S ; Schmitt, Nicole ; Snyders, Dirk J. / The anticonvulsant retigabine suppresses neuronal Kv2-mediated currents. In: Scientific Reports. 2016 ; Vol. 6.

Bibtex

@article{6a6730b17faf428fbd0b3332250780c1,
title = "The anticonvulsant retigabine suppresses neuronal Kv2-mediated currents",
abstract = "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.",
author = "Stas, {Jeroen I} and Elke Bocksteins and Jensen, {Camilla S} and Nicole Schmitt and Snyders, {Dirk J}",
year = "2016",
month = "10",
day = "13",
doi = "10.1038/srep35080",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - The anticonvulsant retigabine suppresses neuronal Kv2-mediated currents

AU - Stas, Jeroen I

AU - Bocksteins, Elke

AU - Jensen, Camilla S

AU - Schmitt, Nicole

AU - Snyders, Dirk J

PY - 2016/10/13

Y1 - 2016/10/13

N2 - 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.

AB - 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.

U2 - 10.1038/srep35080

DO - 10.1038/srep35080

M3 - Journal article

C2 - 27734968

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 35080

ER -

ID: 167356343