Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells

Bupivacaine is a local anesthetic compound belonging to the amino amide group. Its anesthetic effect is commonly related to its inhibitory effect on voltage-gated sodium channels. However, several studies have shown that this drug can also inhibit voltage-operated K+ channels by a different blocking...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Martín, Pedro, Enrique, Nicolás Jorge, Roldán Palomo, Ana Rocío, Rebolledo, Alejandro, Milesi, María Verónica
Formato: Articulo
Lenguaje:Inglés
Publicado: 2012
Materias:
Biología
Bupivacaine
Human umbilical artery
Native vascular smooth muscle
Patch clamp
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/84229
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-84229
record_format dspace
spelling I19-R120-10915-842292024-06-14T18:49:51Z http://sedici.unlp.edu.ar/handle/10915/84229 Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells Martín, Pedro Enrique, Nicolás Jorge Roldán Palomo, Ana Rocío Rebolledo, Alejandro Milesi, María Verónica 2012 2019-10-28T16:23:52Z en Biología Bupivacaine Human umbilical artery Native vascular smooth muscle Patch clamp Bupivacaine is a local anesthetic compound belonging to the amino amide group. Its anesthetic effect is commonly related to its inhibitory effect on voltage-gated sodium channels. However, several studies have shown that this drug can also inhibit voltage-operated K+ channels by a different blocking mechanism. This could explain the observed contractile effects of bupivacaine on blood vessels. Up to now, there were no previous reports in the literature about bupivacaine effects on large conductance voltage- and Ca2+-activated K+ channels (BKCa). Using the patch-clamp technique, it is shown that bupivacaine inhibits single-channel and whole-cell K+ currents carried by BKCa channels in smooth muscle cells isolated from human umbilical artery (HUA). At the single-channel level bupivacaine produced, in a concentration- and voltage-dependent manner (IC50 324 μM at +80 mV), a reduction of single-channel current amplitude and induced a flickery mode of the open channel state. Bupivacaine (300 μM) can also block whole-cell K+ currents (∼45% blockage) in which, under our working conditions, BKCa is the main component. This study presents a new inhibitory effect of bupivacaine on an ion channel involved in different cell functions. Hence, the inhibitory effect of bupivacaine on BKCa channel activity could affect different physiological functions where these channels are involved. Since bupivacaine is commonly used during labor and delivery, its effects on umbilical arteries, where this channel is highly expressed, should be taken into account. Facultad de Ciencias Exactas Articulo Articulo http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf 174-180
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Bupivacaine
Human umbilical artery
Native vascular smooth muscle
Patch clamp
spellingShingle Biología
Bupivacaine
Human umbilical artery
Native vascular smooth muscle
Patch clamp
Martín, Pedro
Enrique, Nicolás Jorge
Roldán Palomo, Ana Rocío
Rebolledo, Alejandro
Milesi, María Verónica
Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells
topic_facet Biología
Bupivacaine
Human umbilical artery
Native vascular smooth muscle
Patch clamp
description Bupivacaine is a local anesthetic compound belonging to the amino amide group. Its anesthetic effect is commonly related to its inhibitory effect on voltage-gated sodium channels. However, several studies have shown that this drug can also inhibit voltage-operated K+ channels by a different blocking mechanism. This could explain the observed contractile effects of bupivacaine on blood vessels. Up to now, there were no previous reports in the literature about bupivacaine effects on large conductance voltage- and Ca2+-activated K+ channels (BKCa). Using the patch-clamp technique, it is shown that bupivacaine inhibits single-channel and whole-cell K+ currents carried by BKCa channels in smooth muscle cells isolated from human umbilical artery (HUA). At the single-channel level bupivacaine produced, in a concentration- and voltage-dependent manner (IC50 324 μM at +80 mV), a reduction of single-channel current amplitude and induced a flickery mode of the open channel state. Bupivacaine (300 μM) can also block whole-cell K+ currents (∼45% blockage) in which, under our working conditions, BKCa is the main component. This study presents a new inhibitory effect of bupivacaine on an ion channel involved in different cell functions. Hence, the inhibitory effect of bupivacaine on BKCa channel activity could affect different physiological functions where these channels are involved. Since bupivacaine is commonly used during labor and delivery, its effects on umbilical arteries, where this channel is highly expressed, should be taken into account.
format Articulo
Articulo
author Martín, Pedro
Enrique, Nicolás Jorge
Roldán Palomo, Ana Rocío
Rebolledo, Alejandro
Milesi, María Verónica
author_facet Martín, Pedro
Enrique, Nicolás Jorge
Roldán Palomo, Ana Rocío
Rebolledo, Alejandro
Milesi, María Verónica
author_sort Martín, Pedro
title Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells
title_short Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells
title_full Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells
title_fullStr Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells
title_full_unstemmed Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells
title_sort bupivacaine inhibits large conductance, voltage- and ca2+- activated k+ channels in human umbilical artery smooth muscle cells
publishDate 2012
url http://sedici.unlp.edu.ar/handle/10915/84229
work_keys_str_mv AT martinpedro bupivacaineinhibitslargeconductancevoltageandca2activatedkchannelsinhumanumbilicalarterysmoothmusclecells
AT enriquenicolasjorge bupivacaineinhibitslargeconductancevoltageandca2activatedkchannelsinhumanumbilicalarterysmoothmusclecells
AT roldanpalomoanarocio bupivacaineinhibitslargeconductancevoltageandca2activatedkchannelsinhumanumbilicalarterysmoothmusclecells
AT rebolledoalejandro bupivacaineinhibitslargeconductancevoltageandca2activatedkchannelsinhumanumbilicalarterysmoothmusclecells
AT milesimariaveronica bupivacaineinhibitslargeconductancevoltageandca2activatedkchannelsinhumanumbilicalarterysmoothmusclecells
_version_ 1807220448999505920

Ejemplares similares