Pharmacological rescue of mutated K(v)3.1 ion-channel linked to progressive myoclonus epilepsies

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Pharmacological rescue of mutated K(v)3.1 ion-channel linked to progressive myoclonus epilepsies. / Munch, Anders Sonne; Saljic, Arnela; Boddum, Kim; Grunnet, Morten; Hougaard, Charlotte; Jespersen, Thomas.

In: European Journal of Pharmacology, Vol. 833, 2018, p. 255-262.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Munch, AS, Saljic, A, Boddum, K, Grunnet, M, Hougaard, C & Jespersen, T 2018, 'Pharmacological rescue of mutated K(v)3.1 ion-channel linked to progressive myoclonus epilepsies', European Journal of Pharmacology, vol. 833, pp. 255-262. https://doi.org/10.1016/j.ejphar.2018.06.015

APA

Munch, A. S., Saljic, A., Boddum, K., Grunnet, M., Hougaard, C., & Jespersen, T. (2018). Pharmacological rescue of mutated K(v)3.1 ion-channel linked to progressive myoclonus epilepsies. European Journal of Pharmacology, 833, 255-262. https://doi.org/10.1016/j.ejphar.2018.06.015

Vancouver

Munch AS, Saljic A, Boddum K, Grunnet M, Hougaard C, Jespersen T. Pharmacological rescue of mutated K(v)3.1 ion-channel linked to progressive myoclonus epilepsies. European Journal of Pharmacology. 2018;833:255-262. https://doi.org/10.1016/j.ejphar.2018.06.015

Author

Munch, Anders Sonne ; Saljic, Arnela ; Boddum, Kim ; Grunnet, Morten ; Hougaard, Charlotte ; Jespersen, Thomas. / Pharmacological rescue of mutated K(v)3.1 ion-channel linked to progressive myoclonus epilepsies. In: European Journal of Pharmacology. 2018 ; Vol. 833. pp. 255-262.

Bibtex

@article{74fbcf0ebafa4d8eb5a31710773032b2,
title = "Pharmacological rescue of mutated K(v)3.1 ion-channel linked to progressive myoclonus epilepsies",
abstract = "Progressive myoclonus epilepsies (PMEs) constitute a cluster of inherent, genetically diverse, rare seizure disorders characterized by ataxia, tonic-clonic seizures, and action myoclonus. Recently, a mutation in the KCNC1 gene (Arg320His) was described in a group of PME patients. The KCNC1 gene encodes the K(v)3.1 potassium ion channel responsible for the rapid repolarization of the membrane potential following action potential firing in fast spiking GABAergic interneurons (FSI), thereby enabling high firing frequency. In the present study, we demonstrate that the Arg320His mutation cause a reduction in the K(v)3.1 current amplitude and acts in a dominantly negative fashion. The mutation profoundly affects channel activation and deactivation kinetics, and we further find that it impairs recruitment of the K(v)3.1 channel to the plasma membrane. The K(v)3 activating compound, RE01, partly rescues the electrophysiological deficit, suggesting that pharmacological activation of K(v)3.1 activity might be a feasible approach for treatment of this cohort of PME patients.",
keywords = "PME, K(v)3.1, MEAK, K(v)3 modulation, KCNC1, RE01, AUT 1",
author = "Munch, {Anders Sonne} and Arnela Saljic and Kim Boddum and Morten Grunnet and Charlotte Hougaard and Thomas Jespersen",
year = "2018",
doi = "10.1016/j.ejphar.2018.06.015",
language = "English",
volume = "833",
pages = "255--262",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Pharmacological rescue of mutated K(v)3.1 ion-channel linked to progressive myoclonus epilepsies

AU - Munch, Anders Sonne

AU - Saljic, Arnela

AU - Boddum, Kim

AU - Grunnet, Morten

AU - Hougaard, Charlotte

AU - Jespersen, Thomas

PY - 2018

Y1 - 2018

N2 - Progressive myoclonus epilepsies (PMEs) constitute a cluster of inherent, genetically diverse, rare seizure disorders characterized by ataxia, tonic-clonic seizures, and action myoclonus. Recently, a mutation in the KCNC1 gene (Arg320His) was described in a group of PME patients. The KCNC1 gene encodes the K(v)3.1 potassium ion channel responsible for the rapid repolarization of the membrane potential following action potential firing in fast spiking GABAergic interneurons (FSI), thereby enabling high firing frequency. In the present study, we demonstrate that the Arg320His mutation cause a reduction in the K(v)3.1 current amplitude and acts in a dominantly negative fashion. The mutation profoundly affects channel activation and deactivation kinetics, and we further find that it impairs recruitment of the K(v)3.1 channel to the plasma membrane. The K(v)3 activating compound, RE01, partly rescues the electrophysiological deficit, suggesting that pharmacological activation of K(v)3.1 activity might be a feasible approach for treatment of this cohort of PME patients.

AB - Progressive myoclonus epilepsies (PMEs) constitute a cluster of inherent, genetically diverse, rare seizure disorders characterized by ataxia, tonic-clonic seizures, and action myoclonus. Recently, a mutation in the KCNC1 gene (Arg320His) was described in a group of PME patients. The KCNC1 gene encodes the K(v)3.1 potassium ion channel responsible for the rapid repolarization of the membrane potential following action potential firing in fast spiking GABAergic interneurons (FSI), thereby enabling high firing frequency. In the present study, we demonstrate that the Arg320His mutation cause a reduction in the K(v)3.1 current amplitude and acts in a dominantly negative fashion. The mutation profoundly affects channel activation and deactivation kinetics, and we further find that it impairs recruitment of the K(v)3.1 channel to the plasma membrane. The K(v)3 activating compound, RE01, partly rescues the electrophysiological deficit, suggesting that pharmacological activation of K(v)3.1 activity might be a feasible approach for treatment of this cohort of PME patients.

KW - PME

KW - K(v)3.1

KW - MEAK

KW - K(v)3 modulation

KW - KCNC1

KW - RE01

KW - AUT 1

U2 - 10.1016/j.ejphar.2018.06.015

DO - 10.1016/j.ejphar.2018.06.015

M3 - Journal article

C2 - 29894724

VL - 833

SP - 255

EP - 262

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

ER -

ID: 213153770