KChIP2 attenuates cardiac hypertrophy through regulation of Ito and intracellular calcium signaling

Recent evidence shows that the auxiliary subunit KChIP2, which assembles with pore-forming Kv4-subunits, represents a new potential regulator of the cardiac calcium-independent transient outward potassium current ( I to ) density. In hypertrophy and heart failure, KChIP2 expression has been found to...

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Autores principales: Jin, Hongwei, Hadri, Lahouaria, Palomeque, Julieta, Morel, Charlotte, Karakikes, Ioannis, Kaprielian, Roger, Hajjar, Roger J., Lebeche, Djamel
Formato: Articulo Preprint
Lenguaje:Inglés
Publicado: 2010
Materias:
Ciencias Médicas
Cardiac hypertrophy
Cardiac contractility
Kv4 channels
KChIP2
Gene transfer
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/128734
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-128734
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Cardiac hypertrophy
Cardiac contractility
Kv4 channels
KChIP2
Gene transfer
spellingShingle Ciencias Médicas
Cardiac hypertrophy
Cardiac contractility
Kv4 channels
KChIP2
Gene transfer
Jin, Hongwei
Hadri, Lahouaria
Palomeque, Julieta
Morel, Charlotte
Karakikes, Ioannis
Kaprielian, Roger
Hajjar, Roger J.
Lebeche, Djamel
KChIP2 attenuates cardiac hypertrophy through regulation of Ito and intracellular calcium signaling
topic_facet Ciencias Médicas
Cardiac hypertrophy
Cardiac contractility
Kv4 channels
KChIP2
Gene transfer
description Recent evidence shows that the auxiliary subunit KChIP2, which assembles with pore-forming Kv4-subunits, represents a new potential regulator of the cardiac calcium-independent transient outward potassium current ( I to ) density. In hypertrophy and heart failure, KChIP2 expression has been found to be significantly decreased. Our aim was to examine the role of KChIP2 in cardiac hypertrophy and the effect of restoring its expression on electrical remodeling and cardiac mechanical function using a combination of molecular, biochemical and gene targeting approaches. KChIP2 overexpression through gene transfer of Ad.KChIP2 in neonatal cardiomyocytes resulted in a significant increase in I to -channel forming Kv4.2 and Kv4.3 protein levels. In vivo gene transfer of KChIP2 in aortic banded adult rats showed that, compared to sham-operated or Ad.β-gal-transduced hearts, KChIP2 significantly attenuated the developed left ventricular hypertrophy, robustly increased I to densities, shortened action potential duration, and significantly altered myocyte mechanics by shortening contraction amplitudes and maximal rates of contraction and relaxation velocities and decreasing Ca 2+ transients. Interestingly, blocking I to with 4-aminopyridine in KChIP2-overexpressing adult cardiomyocytes significantly increased the Ca 2+ transients to control levels. One-day-old rat pups intracardially transduced with KChIP2 for two months then subjected to aortic banding for 6–8 weeks (to induce hypertrophy) showed similar echocardiographic, electrical and mechanical remodeling parameters. In addition, in cultured adult cardiomyocytes, KChIP2 overexpression increased the expression of Ca 2+ -ATPase (SERCA2a) and sodium calcium exchanger but had no effect on ryanodine receptor 2 or phospholamban expression. In neonatal myocytes, KChIP2 notably reversed Ang II-induced hypertrophic changes in protein synthesis and MAP-kinase activation. It also significantly decreased calcineurin expression, NFATc1 expression and nuclear translocation and its downstream target, MCiP1.4. Altogether, these data show that KChIP2 can attenuate cardiac hypertrophy possibly through modulation of intracellular calcium concentration and calcineurin/NFAT pathway.
format Articulo
Preprint
author Jin, Hongwei
Hadri, Lahouaria
Palomeque, Julieta
Morel, Charlotte
Karakikes, Ioannis
Kaprielian, Roger
Hajjar, Roger J.
Lebeche, Djamel
author_facet Jin, Hongwei
Hadri, Lahouaria
Palomeque, Julieta
Morel, Charlotte
Karakikes, Ioannis
Kaprielian, Roger
Hajjar, Roger J.
Lebeche, Djamel
author_sort Jin, Hongwei
title KChIP2 attenuates cardiac hypertrophy through regulation of Ito and intracellular calcium signaling
title_short KChIP2 attenuates cardiac hypertrophy through regulation of Ito and intracellular calcium signaling
title_full KChIP2 attenuates cardiac hypertrophy through regulation of Ito and intracellular calcium signaling
title_fullStr KChIP2 attenuates cardiac hypertrophy through regulation of Ito and intracellular calcium signaling
title_full_unstemmed KChIP2 attenuates cardiac hypertrophy through regulation of Ito and intracellular calcium signaling
title_sort kchip2 attenuates cardiac hypertrophy through regulation of ito and intracellular calcium signaling
publishDate 2010
url http://sedici.unlp.edu.ar/handle/10915/128734
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