KCNQ4 channel activation by BMS-204352 and retigabine

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Standard

KCNQ4 channel activation by BMS-204352 and retigabine. / Schrøder, Rikke Louise K.; Jespersen, Thomas; Christophersen, P; Strøbaek, D; Jensen, B S; Olesen, S P.

I: Neuropharmacology, Bind 40, Nr. 7, 01.06.2001, s. 888-98.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Schrøder, RLK, Jespersen, T, Christophersen, P, Strøbaek, D, Jensen, BS & Olesen, SP 2001, 'KCNQ4 channel activation by BMS-204352 and retigabine', Neuropharmacology, bind 40, nr. 7, s. 888-98.

APA

Schrøder, R. L. K., Jespersen, T., Christophersen, P., Strøbaek, D., Jensen, B. S., & Olesen, S. P. (2001). KCNQ4 channel activation by BMS-204352 and retigabine. Neuropharmacology, 40(7), 888-98.

Vancouver

Schrøder RLK, Jespersen T, Christophersen P, Strøbaek D, Jensen BS, Olesen SP. KCNQ4 channel activation by BMS-204352 and retigabine. Neuropharmacology. 2001 jun. 1;40(7):888-98.

Author

Schrøder, Rikke Louise K. ; Jespersen, Thomas ; Christophersen, P ; Strøbaek, D ; Jensen, B S ; Olesen, S P. / KCNQ4 channel activation by BMS-204352 and retigabine. I: Neuropharmacology. 2001 ; Bind 40, Nr. 7. s. 888-98.

Bibtex

@article{9d68ea977fd14afaafc759787e923024,
title = "KCNQ4 channel activation by BMS-204352 and retigabine",
abstract = "Activation of potassium channels generally reduces cellular excitability, making potassium channel openers potential drug candidates for the treatment of diseases related to hyperexcitabilty such as epilepsy, neuropathic pain, and neurodegeneration. Two compounds, BMS-204352 and retigabine, presently in clinical trials for the treatment of stroke and epilepsy, respectively, have been proposed to exert their protective action via an activation of potassium channels. Here we show that KCNQ4 channels, stably expressed in HEK293 cells, were activated by retigabine and BMS-204352 in a reversible and concentration-dependent manner in the concentration range 0.1-10 microM. Both compounds shifted the KCNQ4 channel activation curves towards more negative potentials by about 10 mV. Further, the maximal current obtainable at large positive voltages was also increased concentration-dependently by both compounds. Finally, a pronounced slowing of the deactivation kinetics was induced in particular by BMS-204352. The M-current blocker linopirdine inhibited the baseline current, as well as the BMS-204352-induced activation of the KCNQ4 channels. KCNQ2, KCNQ2/Q3, and KCNQ3/Q4 channels were activated to a similar degree as KCNQ4 channels by 10 microM of BMS-204352 and retigabine, respectively. The compounds are, thus, likely to be general activators of M-like currents.",
keywords = "Anticonvulsants, Carbamates, Cell Line, Dose-Response Relationship, Drug, Humans, Indoles, KCNQ Potassium Channels, Phenylenediamines, Potassium Channels, Potassium Channels, Voltage-Gated",
author = "Schr{\o}der, {Rikke Louise K.} and Thomas Jespersen and P Christophersen and D Str{\o}baek and Jensen, {B S} and Olesen, {S P}",
year = "2001",
month = jun,
day = "1",
language = "English",
volume = "40",
pages = "888--98",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Pergamon Press",
number = "7",

}

RIS

TY - JOUR

T1 - KCNQ4 channel activation by BMS-204352 and retigabine

AU - Schrøder, Rikke Louise K.

AU - Jespersen, Thomas

AU - Christophersen, P

AU - Strøbaek, D

AU - Jensen, B S

AU - Olesen, S P

PY - 2001/6/1

Y1 - 2001/6/1

N2 - Activation of potassium channels generally reduces cellular excitability, making potassium channel openers potential drug candidates for the treatment of diseases related to hyperexcitabilty such as epilepsy, neuropathic pain, and neurodegeneration. Two compounds, BMS-204352 and retigabine, presently in clinical trials for the treatment of stroke and epilepsy, respectively, have been proposed to exert their protective action via an activation of potassium channels. Here we show that KCNQ4 channels, stably expressed in HEK293 cells, were activated by retigabine and BMS-204352 in a reversible and concentration-dependent manner in the concentration range 0.1-10 microM. Both compounds shifted the KCNQ4 channel activation curves towards more negative potentials by about 10 mV. Further, the maximal current obtainable at large positive voltages was also increased concentration-dependently by both compounds. Finally, a pronounced slowing of the deactivation kinetics was induced in particular by BMS-204352. The M-current blocker linopirdine inhibited the baseline current, as well as the BMS-204352-induced activation of the KCNQ4 channels. KCNQ2, KCNQ2/Q3, and KCNQ3/Q4 channels were activated to a similar degree as KCNQ4 channels by 10 microM of BMS-204352 and retigabine, respectively. The compounds are, thus, likely to be general activators of M-like currents.

AB - Activation of potassium channels generally reduces cellular excitability, making potassium channel openers potential drug candidates for the treatment of diseases related to hyperexcitabilty such as epilepsy, neuropathic pain, and neurodegeneration. Two compounds, BMS-204352 and retigabine, presently in clinical trials for the treatment of stroke and epilepsy, respectively, have been proposed to exert their protective action via an activation of potassium channels. Here we show that KCNQ4 channels, stably expressed in HEK293 cells, were activated by retigabine and BMS-204352 in a reversible and concentration-dependent manner in the concentration range 0.1-10 microM. Both compounds shifted the KCNQ4 channel activation curves towards more negative potentials by about 10 mV. Further, the maximal current obtainable at large positive voltages was also increased concentration-dependently by both compounds. Finally, a pronounced slowing of the deactivation kinetics was induced in particular by BMS-204352. The M-current blocker linopirdine inhibited the baseline current, as well as the BMS-204352-induced activation of the KCNQ4 channels. KCNQ2, KCNQ2/Q3, and KCNQ3/Q4 channels were activated to a similar degree as KCNQ4 channels by 10 microM of BMS-204352 and retigabine, respectively. The compounds are, thus, likely to be general activators of M-like currents.

KW - Anticonvulsants

KW - Carbamates

KW - Cell Line

KW - Dose-Response Relationship, Drug

KW - Humans

KW - Indoles

KW - KCNQ Potassium Channels

KW - Phenylenediamines

KW - Potassium Channels

KW - Potassium Channels, Voltage-Gated

M3 - Journal article

C2 - 11378159

VL - 40

SP - 888

EP - 898

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 7

ER -

ID: 33018256