Properties of mutated murine α4β2 nicotinic receptors linked to partial epilepsy

Marcela Lipovsek; Paola Plazas; Jessica Savino; Alwin Klaassen; Jim Boulter; Ana Belén Elgoyhen; Eleonora Katz

doi:10.1016/j.neulet.2007.12.061

Properties of mutated murine α4β2 nicotinic receptors linked to partial epilepsy

Marcela Lipovsek, Paola Plazas, Jessica Savino, Alwin Klaassen, Jim Boulter, Ana Belén Elgoyhen, Eleonora Katz

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

We characterized, by electrophysiological methods, two biophysical properties of murine recombinant α4β2 nicotinic acetylcholine receptors (nAChR) bearing a mutation (α4:+L264α4:β2 or α4:S252Fα4:β2) linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Sensitivity to acetylcholine (ACh) was increased by the S252F substitution expressed in heterozygosis (α4:S252Fα4:β2) but was markedly reduced when this mutation was expressed in homozygosis (S252Fα4:β2). ACh sensitivity was not altered by the +L264 insertion. Moreover, receptor desensitization was significantly increased by both mutations expressed in heterozygosis. These results are in general agreement to those of rat and human recombinant receptors bearing the same mutations, thus contributing to validate the use of knock-in mice harboring ADNFLE mutations as models to study this pathology.

Original language	English (US)
Pages (from-to)	165-169
Number of pages	5
Journal	Neuroscience Letters
Volume	434
Issue number	2
DOIs	https://doi.org/10.1016/j.neulet.2007.12.061
State	Published - Mar 28 2008
Externally published	Yes

Keywords

ACh
Desensitization
Epilepsy
Ion channels
Nicotinic receptors

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neulet.2007.12.061

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title = "Properties of mutated murine α4β2 nicotinic receptors linked to partial epilepsy",

abstract = "We characterized, by electrophysiological methods, two biophysical properties of murine recombinant α4β2 nicotinic acetylcholine receptors (nAChR) bearing a mutation (α4:+L264α4:β2 or α4:S252Fα4:β2) linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Sensitivity to acetylcholine (ACh) was increased by the S252F substitution expressed in heterozygosis (α4:S252Fα4:β2) but was markedly reduced when this mutation was expressed in homozygosis (S252Fα4:β2). ACh sensitivity was not altered by the +L264 insertion. Moreover, receptor desensitization was significantly increased by both mutations expressed in heterozygosis. These results are in general agreement to those of rat and human recombinant receptors bearing the same mutations, thus contributing to validate the use of knock-in mice harboring ADNFLE mutations as models to study this pathology.",

keywords = "ACh, Desensitization, Epilepsy, Ion channels, Nicotinic receptors",

author = "Marcela Lipovsek and Paola Plazas and Jessica Savino and Alwin Klaassen and Jim Boulter and Elgoyhen, {Ana Bel{\'e}n} and Eleonora Katz",

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doi = "10.1016/j.neulet.2007.12.061",

language = "English (US)",

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AU - Lipovsek, Marcela

AU - Plazas, Paola

AU - Savino, Jessica

AU - Klaassen, Alwin

AU - Boulter, Jim

AU - Elgoyhen, Ana Belén

AU - Katz, Eleonora

PY - 2008/3/28

Y1 - 2008/3/28

N2 - We characterized, by electrophysiological methods, two biophysical properties of murine recombinant α4β2 nicotinic acetylcholine receptors (nAChR) bearing a mutation (α4:+L264α4:β2 or α4:S252Fα4:β2) linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Sensitivity to acetylcholine (ACh) was increased by the S252F substitution expressed in heterozygosis (α4:S252Fα4:β2) but was markedly reduced when this mutation was expressed in homozygosis (S252Fα4:β2). ACh sensitivity was not altered by the +L264 insertion. Moreover, receptor desensitization was significantly increased by both mutations expressed in heterozygosis. These results are in general agreement to those of rat and human recombinant receptors bearing the same mutations, thus contributing to validate the use of knock-in mice harboring ADNFLE mutations as models to study this pathology.

AB - We characterized, by electrophysiological methods, two biophysical properties of murine recombinant α4β2 nicotinic acetylcholine receptors (nAChR) bearing a mutation (α4:+L264α4:β2 or α4:S252Fα4:β2) linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Sensitivity to acetylcholine (ACh) was increased by the S252F substitution expressed in heterozygosis (α4:S252Fα4:β2) but was markedly reduced when this mutation was expressed in homozygosis (S252Fα4:β2). ACh sensitivity was not altered by the +L264 insertion. Moreover, receptor desensitization was significantly increased by both mutations expressed in heterozygosis. These results are in general agreement to those of rat and human recombinant receptors bearing the same mutations, thus contributing to validate the use of knock-in mice harboring ADNFLE mutations as models to study this pathology.

KW - ACh

KW - Desensitization

KW - Epilepsy

KW - Ion channels

KW - Nicotinic receptors

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ER -

Properties of mutated murine α4β2 nicotinic receptors linked to partial epilepsy

Abstract

Keywords

ASJC Scopus subject areas

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