Arachidonic acid activation of BKCa (Slo1) channels associated to the β1-subunit in human vascular smooth muscle cells

Arachidonic acid (AA) is a polyunsaturated fatty acid involvedin a complex network of cellsignaling. Itis well known that this fatty acid can directly modulate several cellu- lar target structures, among them, ion channels. We explored the effects of AA on high conductance Ca 2+ - and voltage- depen...

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Detalles Bibliográficos
Autores principales: Martín, Pedro, Moncada, Melisa, Enrique, Nicolás Jorge, Asuaje, Agustín, Valdez Capuccino, Juan M., González, Carlos, Milesi, María Verónica
Formato: Articulo
Lenguaje:Inglés
Publicado: 2013
Materias:
Biología
PUFAs
Fatty acid
Omega-6 polyunsaturated fatty acid
Human umbilical artery
Patch-clamp
Single channel
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/145039
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-145039
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
PUFAs
Fatty acid
Omega-6 polyunsaturated fatty acid
Human umbilical artery
Patch-clamp
Single channel
spellingShingle Biología
PUFAs
Fatty acid
Omega-6 polyunsaturated fatty acid
Human umbilical artery
Patch-clamp
Single channel
Martín, Pedro
Moncada, Melisa
Enrique, Nicolás Jorge
Asuaje, Agustín
Valdez Capuccino, Juan M.
González, Carlos
Milesi, María Verónica
Arachidonic acid activation of BKCa (Slo1) channels associated to the β1-subunit in human vascular smooth muscle cells
topic_facet Biología
PUFAs
Fatty acid
Omega-6 polyunsaturated fatty acid
Human umbilical artery
Patch-clamp
Single channel
description Arachidonic acid (AA) is a polyunsaturated fatty acid involvedin a complex network of cellsignaling. Itis well known that this fatty acid can directly modulate several cellu- lar target structures, among them, ion channels. We explored the effects of AA on high conductance Ca 2+ - and voltage- dependent K + channel (BKCa) in vascular smooth muscle cells (VSMCs) where the presence of β1-subunit was functionally demonstrated by lithocholic acid activation. Using patch- clamp technique, we show at the single channel level that 10 μM AA increases the open probability (Po) of BKCa channels tenfold, mainly by a reduction of closed dwell times. AA also induces a left-shift in Po versus voltage curves without modifying their steepness. Furthermore, AA acceler- atesthekineticsofthevoltagechannelactivationbyafourfold reduction in latencies to first channel opening. When AAwas tested on BKCa channel expressed in HEK cells with or without the β1-subunit, activation only occurs in presence of the modulatory subunit. These results contribute to highlight the molecular mechanism of AA-dependent BKCa activation. We conclude that AA itself selectively activates the β1- associated BKCa channel, destabilizing its closed state proba- bly by interacting with the β1-subunit, without modifying the channel voltage sensitivity. Since BKCa channels physiologi- cally contribute to regulation of VSMCs contractility and blood pressure, we used the whole-cell configuration to show that AA is able to activate these channels, inducing significant cell hyperpolarization that can lead to VSMCs relaxation.
format Articulo
Articulo
author Martín, Pedro
Moncada, Melisa
Enrique, Nicolás Jorge
Asuaje, Agustín
Valdez Capuccino, Juan M.
González, Carlos
Milesi, María Verónica
author_facet Martín, Pedro
Moncada, Melisa
Enrique, Nicolás Jorge
Asuaje, Agustín
Valdez Capuccino, Juan M.
González, Carlos
Milesi, María Verónica
author_sort Martín, Pedro
title Arachidonic acid activation of BKCa (Slo1) channels associated to the β1-subunit in human vascular smooth muscle cells
title_short Arachidonic acid activation of BKCa (Slo1) channels associated to the β1-subunit in human vascular smooth muscle cells
title_full Arachidonic acid activation of BKCa (Slo1) channels associated to the β1-subunit in human vascular smooth muscle cells
title_fullStr Arachidonic acid activation of BKCa (Slo1) channels associated to the β1-subunit in human vascular smooth muscle cells
title_full_unstemmed Arachidonic acid activation of BKCa (Slo1) channels associated to the β1-subunit in human vascular smooth muscle cells
title_sort arachidonic acid activation of bkca (slo1) channels associated to the β1-subunit in human vascular smooth muscle cells
publishDate 2013
url http://sedici.unlp.edu.ar/handle/10915/145039
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AT enriquenicolasjorge arachidonicacidactivationofbkcaslo1channelsassociatedtotheb1subunitinhumanvascularsmoothmusclecells
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bdutipo_str Repositorios
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