KV1.5–KV 1.3 Recycling Is PKC-Dependent

KV1.5 channel function is modified by different regulatory subunits. KVβ1.3 subunits assemble with KV1.5 channels and induce a fast and incomplete inactivation. Inhibition of PKC abolishes the KVβ1.3-induced fast inactivation, decreases the amplitude of the current KV1.5–KVβ1.3 and modifies their ph...

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Detalhes bibliográficos
Autores: Macias, Alvaro, Cruz, Alicia de la, Peraza, Diego A., Benito-Bueno, Angela de, González Gallego, Teresa, Valenzuela, Carmen
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/698086
Acesso em linha:http://hdl.handle.net/10486/698086
https://dx.doi.org/10.3390/ijms22031336
Access Level:acceso abierto
Palavra-chave:Bisindolylmaleimide II
Calphostin C
K 1.5 V
K β1.3 V
PKC
RACK1
Traffic
Enfermería
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oai_identifier_str oai:repositorio.uam.es:10486/698086
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repository_id_str
spelling KV1.5–KV 1.3 Recycling Is PKC-DependentMacias, AlvaroCruz, Alicia de laPeraza, Diego A.Benito-Bueno, Angela deGonzález Gallego, TeresaValenzuela, CarmenBisindolylmaleimide IICalphostin CK 1.5 VK β1.3 VPKCRACK1TrafficEnfermeríaKV1.5 channel function is modified by different regulatory subunits. KVβ1.3 subunits assemble with KV1.5 channels and induce a fast and incomplete inactivation. Inhibition of PKC abolishes the KVβ1.3-induced fast inactivation, decreases the amplitude of the current KV1.5–KVβ1.3 and modifies their pharmacology likely due to changes in the traffic of KV1.5–KVβ1.3 channels in a PKC-dependent manner. In order to analyze this hypothesis, HEK293 cells were transfected with KV1.5–KVβ1.3 channels, and currents were recorded by whole-cell configuration of the patch-clamp technique. The presence of KV1.5 in the membrane was analyzed by biotinylation techniques, live cell imaging and confocal microscopy approaches. PKC inhibition resulted in a decrease of 33 ± 7% of channels in the cell surface due to reduced recycling to the plasma membrane, as was confirmed by confocal microscopy. Live cell imaging indicated that PKC inhibition almost abolished the recycling of the KV1.5–KVβ1.3 channels, generating an accumulation of channels into the cytoplasm. All these results suggest that the trafficking regulation of KV1.5–KVβ1.3 channels is dependent on phosphorylation by PKC and, therefore, they could represent a clinically relevant issue, mainly in those diseases that exhibit modifications in PKC activity.This research was funded by Ministerio de Ciencia e Innovación (MICINN) Spain SAF2016-75021-R and PID2019-104366RB-C21 (to C.V. and T.G.), the Instituto de Salud Carlos III CIBERCV program CB/11/00222 (to C.V.), and the Consejo Superior de Investigaciones Científicas grants: PIE 201820E104 and 2019AEP148 (to C.V.). The cost of this publication was paid in part by funds from the European Fund for Economic and Regional Development (FEDER). A.M. holds a postdoctoral contract at CNIC. A.d.l.C. and D.A.P. held CSIC contracts. A.d.B.-B. holds an MICINN predoctoral contract (BES-2017-080184)MDPI, Basel, SwitzerlandDepartamento de EnfermeríaFacultad de MedicinaInstituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)Instituto de Investigación Sanitaria del Hospital Universitario de La Paz (IdiPAZ)20212021-01-29research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/698086https://dx.doi.org/10.3390/ijms22031336reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6980862026-06-23T12:46:27Z
dc.title.none.fl_str_mv KV1.5–KV 1.3 Recycling Is PKC-Dependent
title KV1.5–KV 1.3 Recycling Is PKC-Dependent
spellingShingle KV1.5–KV 1.3 Recycling Is PKC-Dependent
Macias, Alvaro
Bisindolylmaleimide II
Calphostin C
K 1.5 V
K β1.3 V
PKC
RACK1
Traffic
Enfermería
title_short KV1.5–KV 1.3 Recycling Is PKC-Dependent
title_full KV1.5–KV 1.3 Recycling Is PKC-Dependent
title_fullStr KV1.5–KV 1.3 Recycling Is PKC-Dependent
title_full_unstemmed KV1.5–KV 1.3 Recycling Is PKC-Dependent
title_sort KV1.5–KV 1.3 Recycling Is PKC-Dependent
dc.creator.none.fl_str_mv Macias, Alvaro
Cruz, Alicia de la
Peraza, Diego A.
Benito-Bueno, Angela de
González Gallego, Teresa
Valenzuela, Carmen
author Macias, Alvaro
author_facet Macias, Alvaro
Cruz, Alicia de la
Peraza, Diego A.
Benito-Bueno, Angela de
González Gallego, Teresa
Valenzuela, Carmen
author_role author
author2 Cruz, Alicia de la
Peraza, Diego A.
Benito-Bueno, Angela de
González Gallego, Teresa
Valenzuela, Carmen
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Enfermería
Facultad de Medicina
Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)
Instituto de Investigación Sanitaria del Hospital Universitario de La Paz (IdiPAZ)
dc.subject.none.fl_str_mv Bisindolylmaleimide II
Calphostin C
K 1.5 V
K β1.3 V
PKC
RACK1
Traffic
Enfermería
topic Bisindolylmaleimide II
Calphostin C
K 1.5 V
K β1.3 V
PKC
RACK1
Traffic
Enfermería
description KV1.5 channel function is modified by different regulatory subunits. KVβ1.3 subunits assemble with KV1.5 channels and induce a fast and incomplete inactivation. Inhibition of PKC abolishes the KVβ1.3-induced fast inactivation, decreases the amplitude of the current KV1.5–KVβ1.3 and modifies their pharmacology likely due to changes in the traffic of KV1.5–KVβ1.3 channels in a PKC-dependent manner. In order to analyze this hypothesis, HEK293 cells were transfected with KV1.5–KVβ1.3 channels, and currents were recorded by whole-cell configuration of the patch-clamp technique. The presence of KV1.5 in the membrane was analyzed by biotinylation techniques, live cell imaging and confocal microscopy approaches. PKC inhibition resulted in a decrease of 33 ± 7% of channels in the cell surface due to reduced recycling to the plasma membrane, as was confirmed by confocal microscopy. Live cell imaging indicated that PKC inhibition almost abolished the recycling of the KV1.5–KVβ1.3 channels, generating an accumulation of channels into the cytoplasm. All these results suggest that the trafficking regulation of KV1.5–KVβ1.3 channels is dependent on phosphorylation by PKC and, therefore, they could represent a clinically relevant issue, mainly in those diseases that exhibit modifications in PKC activity.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-29
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/698086
https://dx.doi.org/10.3390/ijms22031336
url http://hdl.handle.net/10486/698086
https://dx.doi.org/10.3390/ijms22031336
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI, Basel, Switzerland
publisher.none.fl_str_mv MDPI, Basel, Switzerland
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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