Inositol 1,4,5-trisphosphate receptors in the heart

Inositol 1,4,5-trisphosphate (InsP3) is an established calcium-mobilizing messenger, which is well-known to activate Ca2+ signaling in many cell types. Contractile cardiomyocytes express hormone receptors that are coupled to the production of InsP3. Such cardioactive hormones, including endothelin,...

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Main Authors: LAUREN MACKENZIE, H. LLEWELYN RODERICK, ANDREW PROVEN, STUART J CONWAY, MARTIN D BOOTMAN
Format: Article
Language:English
Published: BMC 2004-01-01
Series:Biological Research
Subjects:
Online Access:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400008
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author LAUREN MACKENZIE
H. LLEWELYN RODERICK
ANDREW PROVEN
STUART J CONWAY
MARTIN D BOOTMAN
author_facet LAUREN MACKENZIE
H. LLEWELYN RODERICK
ANDREW PROVEN
STUART J CONWAY
MARTIN D BOOTMAN
author_sort LAUREN MACKENZIE
collection DOAJ
description Inositol 1,4,5-trisphosphate (InsP3) is an established calcium-mobilizing messenger, which is well-known to activate Ca2+ signaling in many cell types. Contractile cardiomyocytes express hormone receptors that are coupled to the production of InsP3. Such cardioactive hormones, including endothelin, may have profound inotropic and arrhythmogenic actions, but it is unclear whether InsP3 underlies any of these effects. We have examined the expression and localization of InsP3 receptors (InsP3Rs), and the potential role of InsP3 in modulating cardiac excitation-contraction coupling (EC coupling). Stimulation of electrically-paced atrial and ventricular myocytes with a membrane-permeant InsP3 ester was found to evoke an increase in the amplitudes of action potential-evoked Ca2+ transients and to cause pro-arrhythmic diastolic Ca2+ transients. All the effects of the InsP3 ester could be blocked using a membrane-permeant antagonist of InsP3Rs (2-aminoethoxydiphenyl borate; 2-APB). Furthermore, 2-APB blocked arrhythmias evoked by endothelin and delayed the onset of positive inotropic responses. Our data indicate that atrial and ventricular cardiomyocytes express functional InsP3Rs, and these channels have the potential to influence EC coupling.
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spelling doaj.art-05dde9305bcc4d1db54668b9d4f46bba2022-12-21T23:46:44ZengBMCBiological Research0716-97600717-62872004-01-01374553557Inositol 1,4,5-trisphosphate receptors in the heartLAUREN MACKENZIEH. LLEWELYN RODERICKANDREW PROVENSTUART J CONWAYMARTIN D BOOTMANInositol 1,4,5-trisphosphate (InsP3) is an established calcium-mobilizing messenger, which is well-known to activate Ca2+ signaling in many cell types. Contractile cardiomyocytes express hormone receptors that are coupled to the production of InsP3. Such cardioactive hormones, including endothelin, may have profound inotropic and arrhythmogenic actions, but it is unclear whether InsP3 underlies any of these effects. We have examined the expression and localization of InsP3 receptors (InsP3Rs), and the potential role of InsP3 in modulating cardiac excitation-contraction coupling (EC coupling). Stimulation of electrically-paced atrial and ventricular myocytes with a membrane-permeant InsP3 ester was found to evoke an increase in the amplitudes of action potential-evoked Ca2+ transients and to cause pro-arrhythmic diastolic Ca2+ transients. All the effects of the InsP3 ester could be blocked using a membrane-permeant antagonist of InsP3Rs (2-aminoethoxydiphenyl borate; 2-APB). Furthermore, 2-APB blocked arrhythmias evoked by endothelin and delayed the onset of positive inotropic responses. Our data indicate that atrial and ventricular cardiomyocytes express functional InsP3Rs, and these channels have the potential to influence EC coupling.http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400008Calciumcardiacinositolarrhythmiaryanodine
spellingShingle LAUREN MACKENZIE
H. LLEWELYN RODERICK
ANDREW PROVEN
STUART J CONWAY
MARTIN D BOOTMAN
Inositol 1,4,5-trisphosphate receptors in the heart
Biological Research
Calcium
cardiac
inositol
arrhythmia
ryanodine
title Inositol 1,4,5-trisphosphate receptors in the heart
title_full Inositol 1,4,5-trisphosphate receptors in the heart
title_fullStr Inositol 1,4,5-trisphosphate receptors in the heart
title_full_unstemmed Inositol 1,4,5-trisphosphate receptors in the heart
title_short Inositol 1,4,5-trisphosphate receptors in the heart
title_sort inositol 1 4 5 trisphosphate receptors in the heart
topic Calcium
cardiac
inositol
arrhythmia
ryanodine
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400008
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