Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II

Returning to normal pH after acidosis, similar to reperfusion after ischemia, is prone to arrhythmias. The type and mechanisms of these arrhythmias have never been explored and were the aim of the present work. Langendorff-perfused rat/mice hearts and rat-isolated myocytes were subjected to respirat...

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Autores principales: Said, María Matilde, Becerra, Romina Valeria, Palomeque, Julieta, Rinaldi, Gustavo, Kaetzel, M. A., Diaz-Sylvester, P. L., Copello, J. A., Dedman, J. R., Mundiña-Weilenmann, Cecilia, Vittone, Leticia, Mattiazzi, Alicia Ramona
Formato: Articulo
Lenguaje:Español
Publicado: 2008
Materias:
Ciencias Médicas
sarcoplasmic reticulum
calcium/calmodulin-dependent protein kinase
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/106844
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC2593495&blobtype=pdf
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SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-106844
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Español
topic Ciencias Médicas
sarcoplasmic reticulum
calcium/calmodulin-dependent protein kinase
spellingShingle Ciencias Médicas
sarcoplasmic reticulum
calcium/calmodulin-dependent protein kinase
Said, María Matilde
Becerra, Romina Valeria
Palomeque, Julieta
Rinaldi, Gustavo
Kaetzel, M. A.
Diaz-Sylvester, P. L.
Copello, J. A.
Dedman, J. R.
Mundiña-Weilenmann, Cecilia
Vittone, Leticia
Mattiazzi, Alicia Ramona
Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
topic_facet Ciencias Médicas
sarcoplasmic reticulum
calcium/calmodulin-dependent protein kinase
description Returning to normal pH after acidosis, similar to reperfusion after ischemia, is prone to arrhythmias. The type and mechanisms of these arrhythmias have never been explored and were the aim of the present work. Langendorff-perfused rat/mice hearts and rat-isolated myocytes were subjected to respiratory acidosis and then returned to normal pH. Monophasic action potentials and left ventricular developed pressure were recorded. The removal of acidosis provoked ectopic beats that were blunted by 1 mM of the CaMKII inhibitor KN-93, 1 mM thapsigargin, to inhibit sarcoplasmic reticulum (SR) Ca21 uptake, and 30 nM ryanodine or 45 mM dantrolene, to inhibit SR Ca21 release and were not observed in a transgenic mouse model with inhibition of CaMKII targeted to the SR. Acidosis increased the phosphorylation of Thr17 site of phospholamban (PT-PLN) and SR Ca21 load. Both effects were precluded by KN-93. The return to normal pH was associated with an increase in SR Ca21 leak, when compared with that of control or with acidosis at the same SR Ca21 content. Ca21 leak occurred without changes in the phosphorylation of ryanodine receptors type 2 (RyR2) and was blunted by KN-93. Experiments in planar lipid bilayers confirmed the reversible inhibitory effect of acidosis on RyR2. Ectopic activity was triggered by membrane depolarizations (delayed afterdepolarizations), primarily occurring in epicardium and were prevented by KN-93. The results reveal that arrhythmias after acidosis are dependent on CaMKII activation and are associated with an increase in SR Ca21 load, which appears to be mainly due to the increase in PT-PLN.
format Articulo
Articulo
author Said, María Matilde
Becerra, Romina Valeria
Palomeque, Julieta
Rinaldi, Gustavo
Kaetzel, M. A.
Diaz-Sylvester, P. L.
Copello, J. A.
Dedman, J. R.
Mundiña-Weilenmann, Cecilia
Vittone, Leticia
Mattiazzi, Alicia Ramona
author_facet Said, María Matilde
Becerra, Romina Valeria
Palomeque, Julieta
Rinaldi, Gustavo
Kaetzel, M. A.
Diaz-Sylvester, P. L.
Copello, J. A.
Dedman, J. R.
Mundiña-Weilenmann, Cecilia
Vittone, Leticia
Mattiazzi, Alicia Ramona
author_sort Said, María Matilde
title Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
title_short Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
title_full Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
title_fullStr Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
title_full_unstemmed Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
title_sort increased intracellular ca2+ and sr ca2+ load contribute to arrhythmias after acidosis in rat heart : role of ca2+/calmodulin-dependent protein kinase ii
publishDate 2008
url http://sedici.unlp.edu.ar/handle/10915/106844
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC2593495&blobtype=pdf
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