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

dc.creatorMartín, Pedro
dc.creatorMoncada, Melisa
dc.creatorEnrique, Nicolás Jorge
dc.creatorAsuaje, Agustín
dc.creatorValdez Capuccino, Juan M.
dc.creatorGonzález, Carlos
dc.creatorMilesi, María Verónica
dc.date2013-12-28
dc.date2022-11-02T17:40:53Z
dc.date.accessioned2023-07-15T04:57:38Z
dc.date.available2023-07-15T04:57:38Z
dc.identifierhttp://sedici.unlp.edu.ar/handle/10915/145039
dc.identifierissn:1432-2013
dc.identifierissn:0031-6768
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/7471548
dc.descriptionArachidonic 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.
dc.descriptionGrupo de Investigación en Fisiología Vascular
dc.formatapplication/pdf
dc.format1779-1792
dc.languageen
dc.rightshttp://creativecommons.org/licenses/by/4.0/
dc.rightsCreative Commons Attribution 4.0 International (CC BY 4.0)
dc.subjectBiología
dc.subjectPUFAs
dc.subjectFatty acid
dc.subjectOmega-6 polyunsaturated fatty acid
dc.subjectHuman umbilical artery
dc.subjectPatch-clamp
dc.subjectSingle channel
dc.titleArachidonic acid activation of BKCa (Slo1) channels associated to the β1-subunit in human vascular smooth muscle cells
dc.typeArticulo
dc.typeArticulo


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