Identification of Navβ1 residues involved in the modulation of the sodium channel Nav1.4.

Voltage-gated sodium channels (VGSCs) are heteromeric protein complexes that initiate action potentials in excitable cells. The voltage-gated sodium channel accessory subunit, Navβ1, allosterically modulates the α subunit pore structure upon binding. To date, the molecular determinants of the interf...

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Autores principales:	Angel A Islas, Alfredo Sánchez-Solano, Thomas Scior, Lourdes Millan-PerezPeña, Eduardo M Salinas-Stefanon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a80c5e775e9142e792eb26e42d08ba1e
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spelling	oai:doaj.org-article:a80c5e775e9142e792eb26e42d08ba1e2021-11-18T08:41:52ZIdentification of Navβ1 residues involved in the modulation of the sodium channel Nav1.4.1932-620310.1371/journal.pone.0081995https://doaj.org/article/a80c5e775e9142e792eb26e42d08ba1e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24358138/?tool=EBIhttps://doaj.org/toc/1932-6203Voltage-gated sodium channels (VGSCs) are heteromeric protein complexes that initiate action potentials in excitable cells. The voltage-gated sodium channel accessory subunit, Navβ1, allosterically modulates the α subunit pore structure upon binding. To date, the molecular determinants of the interface remain unknown. We made use of sequence, knowledge and structure-based methods to identify residues critical to the association of the α and β1 Nav1.4 subunits. The Navβ1 point mutant C43A disrupted the modulation of voltage dependence of activation and inactivation and delayed the peak current decay, the recovery from inactivation, and induced a use-dependent decay upon depolarisation at 1 Hz. The Navβ1 mutant R89A selectively delayed channel inactivation and recovery from inactivation and had no effect on voltage dependence or repetitive depolarisations. Navβ1 mutants Y32A and G33M selectively modified the half voltage of inactivation without altering the kinetics. Despite low sequence identity, highly conserved structural elements were identified. Our models were consistent with published data and may help relate pathologies associated with VGSCs to the Navβ1 subunit.Angel A IslasAlfredo Sánchez-SolanoThomas SciorLourdes Millan-PerezPeñaEduardo M Salinas-StefanonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e81995 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Angel A Islas Alfredo Sánchez-Solano Thomas Scior Lourdes Millan-PerezPeña Eduardo M Salinas-Stefanon Identification of Navβ1 residues involved in the modulation of the sodium channel Nav1.4.
description	Voltage-gated sodium channels (VGSCs) are heteromeric protein complexes that initiate action potentials in excitable cells. The voltage-gated sodium channel accessory subunit, Navβ1, allosterically modulates the α subunit pore structure upon binding. To date, the molecular determinants of the interface remain unknown. We made use of sequence, knowledge and structure-based methods to identify residues critical to the association of the α and β1 Nav1.4 subunits. The Navβ1 point mutant C43A disrupted the modulation of voltage dependence of activation and inactivation and delayed the peak current decay, the recovery from inactivation, and induced a use-dependent decay upon depolarisation at 1 Hz. The Navβ1 mutant R89A selectively delayed channel inactivation and recovery from inactivation and had no effect on voltage dependence or repetitive depolarisations. Navβ1 mutants Y32A and G33M selectively modified the half voltage of inactivation without altering the kinetics. Despite low sequence identity, highly conserved structural elements were identified. Our models were consistent with published data and may help relate pathologies associated with VGSCs to the Navβ1 subunit.
format	article
author	Angel A Islas Alfredo Sánchez-Solano Thomas Scior Lourdes Millan-PerezPeña Eduardo M Salinas-Stefanon
author_facet	Angel A Islas Alfredo Sánchez-Solano Thomas Scior Lourdes Millan-PerezPeña Eduardo M Salinas-Stefanon
author_sort	Angel A Islas
title	Identification of Navβ1 residues involved in the modulation of the sodium channel Nav1.4.
title_short	Identification of Navβ1 residues involved in the modulation of the sodium channel Nav1.4.
title_full	Identification of Navβ1 residues involved in the modulation of the sodium channel Nav1.4.
title_fullStr	Identification of Navβ1 residues involved in the modulation of the sodium channel Nav1.4.
title_full_unstemmed	Identification of Navβ1 residues involved in the modulation of the sodium channel Nav1.4.
title_sort	identification of navβ1 residues involved in the modulation of the sodium channel nav1.4.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a80c5e775e9142e792eb26e42d08ba1e
work_keys_str_mv	AT angelaislas identificationofnavb1residuesinvolvedinthemodulationofthesodiumchannelnav14 AT alfredosanchezsolano identificationofnavb1residuesinvolvedinthemodulationofthesodiumchannelnav14 AT thomasscior identificationofnavb1residuesinvolvedinthemodulationofthesodiumchannelnav14 AT lourdesmillanperezpena identificationofnavb1residuesinvolvedinthemodulationofthesodiumchannelnav14 AT eduardomsalinasstefanon identificationofnavb1residuesinvolvedinthemodulationofthesodiumchannelnav14
_version_	1718421463130701824

Identification of Navβ1 residues involved in the modulation of the sodium channel Nav1.4.

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