Cargando…

Abnormal Ca(2+) homeostasis, atrial arrhythmogenesis, and sinus node dysfunction in murine hearts modeling RyR2 modification

Ryanodine receptor type 2 (RyR2) mutations are implicated in catecholaminergic polymorphic ventricular tachycardia (CPVT) thought to result from altered myocyte Ca(2+) homeostasis reflecting inappropriate “leakiness” of RyR2-Ca(2+) release channels arising from increases in their basal activity, alt...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Yanmin, Matthews, Gareth D. K., Lei, Ming, Huang, Christopher L.-H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691467/
https://www.ncbi.nlm.nih.gov/pubmed/23805105
http://dx.doi.org/10.3389/fphys.2013.00150
_version_ 1782274469997314048
author Zhang, Yanmin
Matthews, Gareth D. K.
Lei, Ming
Huang, Christopher L.-H.
author_facet Zhang, Yanmin
Matthews, Gareth D. K.
Lei, Ming
Huang, Christopher L.-H.
author_sort Zhang, Yanmin
collection PubMed
description Ryanodine receptor type 2 (RyR2) mutations are implicated in catecholaminergic polymorphic ventricular tachycardia (CPVT) thought to result from altered myocyte Ca(2+) homeostasis reflecting inappropriate “leakiness” of RyR2-Ca(2+) release channels arising from increases in their basal activity, alterations in their phosphorylation, or defective interactions with other molecules or ions. The latter include calstabin, calsequestrin-2, Mg(2+), and extraluminal or intraluminal Ca(2+). Recent clinical studies additionally associate RyR2 abnormalities with atrial arrhythmias including atrial tachycardia (AT), fibrillation (AF), and standstill, and sinus node dysfunction (SND). Some RyR2 mutations associated with CPVT in mouse models also show such arrhythmias that similarly correlate with altered Ca(2+) homeostasis. Some examples show evidence for increased Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylation of RyR2. A homozygotic RyR2-P2328S variant demonstrates potential arrhythmic substrate resulting from reduced conduction velocity (CV) in addition to delayed afterdepolarizations (DADs) and ectopic action potential (AP) firing. Finally, one model with an increased RyR2 activity in the sino-atrial node (SAN) shows decreased automaticity in the presence of Ca(2+)-dependent decreases in I(Ca, L) and diastolic sarcoplasmic reticular (SR) Ca(2+) depletion.
format Online
Article
Text
id pubmed-3691467
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-36914672013-06-26 Abnormal Ca(2+) homeostasis, atrial arrhythmogenesis, and sinus node dysfunction in murine hearts modeling RyR2 modification Zhang, Yanmin Matthews, Gareth D. K. Lei, Ming Huang, Christopher L.-H. Front Physiol Physiology Ryanodine receptor type 2 (RyR2) mutations are implicated in catecholaminergic polymorphic ventricular tachycardia (CPVT) thought to result from altered myocyte Ca(2+) homeostasis reflecting inappropriate “leakiness” of RyR2-Ca(2+) release channels arising from increases in their basal activity, alterations in their phosphorylation, or defective interactions with other molecules or ions. The latter include calstabin, calsequestrin-2, Mg(2+), and extraluminal or intraluminal Ca(2+). Recent clinical studies additionally associate RyR2 abnormalities with atrial arrhythmias including atrial tachycardia (AT), fibrillation (AF), and standstill, and sinus node dysfunction (SND). Some RyR2 mutations associated with CPVT in mouse models also show such arrhythmias that similarly correlate with altered Ca(2+) homeostasis. Some examples show evidence for increased Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylation of RyR2. A homozygotic RyR2-P2328S variant demonstrates potential arrhythmic substrate resulting from reduced conduction velocity (CV) in addition to delayed afterdepolarizations (DADs) and ectopic action potential (AP) firing. Finally, one model with an increased RyR2 activity in the sino-atrial node (SAN) shows decreased automaticity in the presence of Ca(2+)-dependent decreases in I(Ca, L) and diastolic sarcoplasmic reticular (SR) Ca(2+) depletion. Frontiers Media S.A. 2013-06-25 /pmc/articles/PMC3691467/ /pubmed/23805105 http://dx.doi.org/10.3389/fphys.2013.00150 Text en Copyright © 2013 Zhang, Matthews, Lei and Huang. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Physiology
Zhang, Yanmin
Matthews, Gareth D. K.
Lei, Ming
Huang, Christopher L.-H.
Abnormal Ca(2+) homeostasis, atrial arrhythmogenesis, and sinus node dysfunction in murine hearts modeling RyR2 modification
title Abnormal Ca(2+) homeostasis, atrial arrhythmogenesis, and sinus node dysfunction in murine hearts modeling RyR2 modification
title_full Abnormal Ca(2+) homeostasis, atrial arrhythmogenesis, and sinus node dysfunction in murine hearts modeling RyR2 modification
title_fullStr Abnormal Ca(2+) homeostasis, atrial arrhythmogenesis, and sinus node dysfunction in murine hearts modeling RyR2 modification
title_full_unstemmed Abnormal Ca(2+) homeostasis, atrial arrhythmogenesis, and sinus node dysfunction in murine hearts modeling RyR2 modification
title_short Abnormal Ca(2+) homeostasis, atrial arrhythmogenesis, and sinus node dysfunction in murine hearts modeling RyR2 modification
title_sort abnormal ca(2+) homeostasis, atrial arrhythmogenesis, and sinus node dysfunction in murine hearts modeling ryr2 modification
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691467/
https://www.ncbi.nlm.nih.gov/pubmed/23805105
http://dx.doi.org/10.3389/fphys.2013.00150
work_keys_str_mv AT zhangyanmin abnormalca2homeostasisatrialarrhythmogenesisandsinusnodedysfunctioninmurineheartsmodelingryr2modification
AT matthewsgarethdk abnormalca2homeostasisatrialarrhythmogenesisandsinusnodedysfunctioninmurineheartsmodelingryr2modification
AT leiming abnormalca2homeostasisatrialarrhythmogenesisandsinusnodedysfunctioninmurineheartsmodelingryr2modification
AT huangchristopherlh abnormalca2homeostasisatrialarrhythmogenesisandsinusnodedysfunctioninmurineheartsmodelingryr2modification