The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels.

Bo Hjorth Bentzen; Nicole Schmitt; Kirstine Calloe; William Dalby Brown; Morten Grunnet; Søren-Peter Olesen

doi:10.1016/j.neuropharm.2006.07.001

The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels.

Bo Hjorth Bentzen, Nicole Schmitt, Kirstine Calloe, William Dalby Brown, Morten Grunnet, Søren-Peter Olesen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

84 Citationer (Scopus)

Abstract

Udgivelsesdato: 2006-Nov

Originalsprog	Engelsk
Tidsskrift	Neuropharmacology
Vol/bind	51
Udgave nummer	6
Sider (fra-til)	1068-77
Antal sider	9
ISSN	0028-3908
DOI	https://doi.org/10.1016/j.neuropharm.2006.07.001
Status	Udgivet - 2006

Bibliografisk note

Keywords: Acrylamides; Algorithms; Animals; Binding Sites; DNA, Complementary; Electrophysiology; Humans; KCNQ Potassium Channels; KCNQ1 Potassium Channel; KCNQ2 Potassium Channel; Kinetics; Morpholines; Neurons; Oocytes; Patch-Clamp Techniques; Point Mutation; Tryptophan; Xenopus laevis

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10.1016/j.neuropharm.2006.07.001

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Citationsformater

@article{7a1a2800ab5411ddb5e9000ea68e967b,

title = "The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels.",

abstract = "The family of Kv7 (KCNQ) potassium channels consists of five members. Kv7.2 and 3 are the primary molecular correlates of the M-current, but also Kv7.4 and Kv7.5 display M-current characteristics. M-channel modulators include blockers (e.g., linopirdine) for cognition enhancement and openers (e.g., retigabine) for treatment of epilepsy and neuropathic pain. We investigated the effect of a Bristol-Myers Squibb compound (S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide [(S)-1] on cloned human Kv7.1-5 potassium channels expressed in Xenopus laevis oocytes. Using two-electrode voltage-clamp recordings we found that (S)-1 blocks Kv7.1 and Kv7.1/KCNE1 currents. In contrast, (S)-1 produced a hyperpolarizing shift of the activation curve for Kv7.2, Kv7.2/Kv7.3, Kv7.4 and Kv7.5. Further, the compound enhanced the maximal current amplitude at all potentials for Kv7.4 and Kv7.5 whereas the combined activation/block of Kv7.2 and Kv7.2/3 was strongly voltage-dependent. The tryptophan residue 242 in S5, known to be crucial for the effect of retigabine, was also shown to be critical for the enhancing effect of (S)-1 and BMS204352. Furthermore, no additive effect on Kv7.4 current amplitude was observed when both retigabine and (S)-1 or BMS204352 were applied simultaneously. In conclusion, (S)-1 differentially affects the Kv7 channel subtypes and is dependent on a single tryptophan for the current enhancing effect in Kv7.4.",

author = "Bentzen, {Bo Hjorth} and Nicole Schmitt and Kirstine Calloe and {Dalby Brown}, William and Morten Grunnet and S{\o}ren-Peter Olesen",

note = "Keywords: Acrylamides; Algorithms; Animals; Binding Sites; DNA, Complementary; Electrophysiology; Humans; KCNQ Potassium Channels; KCNQ1 Potassium Channel; KCNQ2 Potassium Channel; Kinetics; Morpholines; Neurons; Oocytes; Patch-Clamp Techniques; Point Mutation; Tryptophan; Xenopus laevis",

year = "2006",

doi = "10.1016/j.neuropharm.2006.07.001",

language = "English",

volume = "51",

pages = "1068--77",

journal = "Neuropharmacology",

issn = "0028-3908",

publisher = "Pergamon Press",

number = "6",

}

TY - JOUR

T1 - The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels.

AU - Bentzen, Bo Hjorth

AU - Schmitt, Nicole

AU - Calloe, Kirstine

AU - Dalby Brown, William

AU - Grunnet, Morten

AU - Olesen, Søren-Peter

N1 - Keywords: Acrylamides; Algorithms; Animals; Binding Sites; DNA, Complementary; Electrophysiology; Humans; KCNQ Potassium Channels; KCNQ1 Potassium Channel; KCNQ2 Potassium Channel; Kinetics; Morpholines; Neurons; Oocytes; Patch-Clamp Techniques; Point Mutation; Tryptophan; Xenopus laevis

PY - 2006

Y1 - 2006

N2 - The family of Kv7 (KCNQ) potassium channels consists of five members. Kv7.2 and 3 are the primary molecular correlates of the M-current, but also Kv7.4 and Kv7.5 display M-current characteristics. M-channel modulators include blockers (e.g., linopirdine) for cognition enhancement and openers (e.g., retigabine) for treatment of epilepsy and neuropathic pain. We investigated the effect of a Bristol-Myers Squibb compound (S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide [(S)-1] on cloned human Kv7.1-5 potassium channels expressed in Xenopus laevis oocytes. Using two-electrode voltage-clamp recordings we found that (S)-1 blocks Kv7.1 and Kv7.1/KCNE1 currents. In contrast, (S)-1 produced a hyperpolarizing shift of the activation curve for Kv7.2, Kv7.2/Kv7.3, Kv7.4 and Kv7.5. Further, the compound enhanced the maximal current amplitude at all potentials for Kv7.4 and Kv7.5 whereas the combined activation/block of Kv7.2 and Kv7.2/3 was strongly voltage-dependent. The tryptophan residue 242 in S5, known to be crucial for the effect of retigabine, was also shown to be critical for the enhancing effect of (S)-1 and BMS204352. Furthermore, no additive effect on Kv7.4 current amplitude was observed when both retigabine and (S)-1 or BMS204352 were applied simultaneously. In conclusion, (S)-1 differentially affects the Kv7 channel subtypes and is dependent on a single tryptophan for the current enhancing effect in Kv7.4.

AB - The family of Kv7 (KCNQ) potassium channels consists of five members. Kv7.2 and 3 are the primary molecular correlates of the M-current, but also Kv7.4 and Kv7.5 display M-current characteristics. M-channel modulators include blockers (e.g., linopirdine) for cognition enhancement and openers (e.g., retigabine) for treatment of epilepsy and neuropathic pain. We investigated the effect of a Bristol-Myers Squibb compound (S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide [(S)-1] on cloned human Kv7.1-5 potassium channels expressed in Xenopus laevis oocytes. Using two-electrode voltage-clamp recordings we found that (S)-1 blocks Kv7.1 and Kv7.1/KCNE1 currents. In contrast, (S)-1 produced a hyperpolarizing shift of the activation curve for Kv7.2, Kv7.2/Kv7.3, Kv7.4 and Kv7.5. Further, the compound enhanced the maximal current amplitude at all potentials for Kv7.4 and Kv7.5 whereas the combined activation/block of Kv7.2 and Kv7.2/3 was strongly voltage-dependent. The tryptophan residue 242 in S5, known to be crucial for the effect of retigabine, was also shown to be critical for the enhancing effect of (S)-1 and BMS204352. Furthermore, no additive effect on Kv7.4 current amplitude was observed when both retigabine and (S)-1 or BMS204352 were applied simultaneously. In conclusion, (S)-1 differentially affects the Kv7 channel subtypes and is dependent on a single tryptophan for the current enhancing effect in Kv7.4.

U2 - 10.1016/j.neuropharm.2006.07.001

DO - 10.1016/j.neuropharm.2006.07.001

M3 - Journal article

C2 - 16904708

SN - 0028-3908

VL - 51

SP - 1068

EP - 1077

JO - Neuropharmacology

JF - Neuropharmacology

IS - 6

ER -