Structure based analysis of KATP channel with a DEND syndrome mutation in murine skeletal muscle

Abstract Developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome, the most severe end of neonatal diabetes mellitus, is caused by mutation in the ATP-sensitive potassium (KATP) channel. In addition to diabetes, DEND patients present muscle weakness as one of the symptoms, and although t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shoichiro Horita, Tomoyuki Ono, Saul Gonzalez-Resines, Yuko Ono, Megumi Yamachi, Songji Zhao, Carmen Domene, Yuko Maejima, Kenju Shimomura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f773962797f64e77ad79d1b308605126
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f773962797f64e77ad79d1b308605126
record_format	dspace
spelling	oai:doaj.org-article:f773962797f64e77ad79d1b3086051262021-12-02T13:24:14ZStructure based analysis of KATP channel with a DEND syndrome mutation in murine skeletal muscle10.1038/s41598-021-86121-52045-2322https://doaj.org/article/f773962797f64e77ad79d1b3086051262021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86121-5https://doaj.org/toc/2045-2322Abstract Developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome, the most severe end of neonatal diabetes mellitus, is caused by mutation in the ATP-sensitive potassium (KATP) channel. In addition to diabetes, DEND patients present muscle weakness as one of the symptoms, and although the muscle weakness is considered to originate in the brain, the pathological effects of mutated KATP channels in skeletal muscle remain elusive. Here, we describe the local effects of the KATP channel on muscle by expressing the mutation present in the KATP channels of the DEND syndrome in the murine skeletal muscle cell line C2C12 in combination with computer simulation. The present study revealed that the DEND mutation can lead to a hyperpolarized state of the muscle cell membrane, and molecular dynamics simulations based on a recently reported high-resolution structure provide an explanation as to why the mutation reduces ATP sensitivity and reveal the changes in the local interactions between ATP molecules and the channel.Shoichiro HoritaTomoyuki OnoSaul Gonzalez-ResinesYuko OnoMegumi YamachiSongji ZhaoCarmen DomeneYuko MaejimaKenju ShimomuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shoichiro Horita Tomoyuki Ono Saul Gonzalez-Resines Yuko Ono Megumi Yamachi Songji Zhao Carmen Domene Yuko Maejima Kenju Shimomura Structure based analysis of KATP channel with a DEND syndrome mutation in murine skeletal muscle
description	Abstract Developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome, the most severe end of neonatal diabetes mellitus, is caused by mutation in the ATP-sensitive potassium (KATP) channel. In addition to diabetes, DEND patients present muscle weakness as one of the symptoms, and although the muscle weakness is considered to originate in the brain, the pathological effects of mutated KATP channels in skeletal muscle remain elusive. Here, we describe the local effects of the KATP channel on muscle by expressing the mutation present in the KATP channels of the DEND syndrome in the murine skeletal muscle cell line C2C12 in combination with computer simulation. The present study revealed that the DEND mutation can lead to a hyperpolarized state of the muscle cell membrane, and molecular dynamics simulations based on a recently reported high-resolution structure provide an explanation as to why the mutation reduces ATP sensitivity and reveal the changes in the local interactions between ATP molecules and the channel.
format	article
author	Shoichiro Horita Tomoyuki Ono Saul Gonzalez-Resines Yuko Ono Megumi Yamachi Songji Zhao Carmen Domene Yuko Maejima Kenju Shimomura
author_facet	Shoichiro Horita Tomoyuki Ono Saul Gonzalez-Resines Yuko Ono Megumi Yamachi Songji Zhao Carmen Domene Yuko Maejima Kenju Shimomura
author_sort	Shoichiro Horita
title	Structure based analysis of KATP channel with a DEND syndrome mutation in murine skeletal muscle
title_short	Structure based analysis of KATP channel with a DEND syndrome mutation in murine skeletal muscle
title_full	Structure based analysis of KATP channel with a DEND syndrome mutation in murine skeletal muscle
title_fullStr	Structure based analysis of KATP channel with a DEND syndrome mutation in murine skeletal muscle
title_full_unstemmed	Structure based analysis of KATP channel with a DEND syndrome mutation in murine skeletal muscle
title_sort	structure based analysis of katp channel with a dend syndrome mutation in murine skeletal muscle
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f773962797f64e77ad79d1b308605126
work_keys_str_mv	AT shoichirohorita structurebasedanalysisofkatpchannelwithadendsyndromemutationinmurineskeletalmuscle AT tomoyukiono structurebasedanalysisofkatpchannelwithadendsyndromemutationinmurineskeletalmuscle AT saulgonzalezresines structurebasedanalysisofkatpchannelwithadendsyndromemutationinmurineskeletalmuscle AT yukoono structurebasedanalysisofkatpchannelwithadendsyndromemutationinmurineskeletalmuscle AT megumiyamachi structurebasedanalysisofkatpchannelwithadendsyndromemutationinmurineskeletalmuscle AT songjizhao structurebasedanalysisofkatpchannelwithadendsyndromemutationinmurineskeletalmuscle AT carmendomene structurebasedanalysisofkatpchannelwithadendsyndromemutationinmurineskeletalmuscle AT yukomaejima structurebasedanalysisofkatpchannelwithadendsyndromemutationinmurineskeletalmuscle AT kenjushimomura structurebasedanalysisofkatpchannelwithadendsyndromemutationinmurineskeletalmuscle
_version_	1718393128543584256

Structure based analysis of KATP channel with a DEND syndrome mutation in murine skeletal muscle

Ejemplares similares