Nuclear translocation of calmodulin in pathological cardiac hypertrophy originates from ryanodine receptor bound calmodulin
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چکیده
منابع مشابه
Cardiac hypertrophy associated with impaired regulation of cardiac ryanodine receptor by calmodulin and S100A1.
The cardiac ryanodine receptor (RyR2) is inhibited by calmodulin (CaM) and S100A1. Simultaneous substitution of three amino acid residues (W3587A, L3591D, F3603A; RyR2ADA) in the CaM binding domain of RyR2 results in loss of CaM inhibition at submicromolar (diastolic) and micromolar (systolic) Ca²⁺, cardiac hypertrophy, and heart failure in Ryr2ADA/ADA mice. To address whether cardiac hypertrop...
متن کاملDissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca(2+) release in heart failure.
AIMS Calmodulin (CaM) is well known to modulate the channel function of the cardiac ryanodine receptor (RyR2). However, the possible role of CaM on the aberrant Ca(2+) release in diseased hearts remains unclear. In this study, we investigated the state of RyR2-bound CaM and channel dysfunctions in pacing-induced failing hearts. METHODS AND RESULTS The characteristics of CaM binding to RyR2 an...
متن کاملAberrant interaction of calmodulin with the ryanodine receptor develops hypertrophy in the neonatal cardiomyocyte.
We have shown previously that the inter-domain interaction between the two domains of RyR (ryanodine receptor), CaMBD [CaM (calmodulin)-binding domain] and CaMLD (CaM-like domain), activates the Ca(2+) channel, and this process is called activation-link formation [Gangopadhyay and Ikemoto (2008) Biochem. J. 411, 415-423]. Thus CaM that is bound to CaMBD is expected to interfere the activation-l...
متن کاملThe Arrhythmogenic Calmodulin p.Phe142Leu Mutation Impairs C-domain Ca2+ Binding but Not Calmodulin-dependent Inhibition of the Cardiac Ryanodine Receptor*
A number of point mutations in the intracellular Ca2+-sensing protein calmodulin (CaM) are arrhythmogenic, yet their underlying mechanisms are not clear. These mutations generally decrease Ca2+ binding to CaM and impair inhibition of CaM-regulated Ca2+ channels like the cardiac Ca2+ release channel (ryanodine receptor, RyR2), and it appears that attenuated CaM Ca2+ binding correlates with impai...
متن کاملCalmodulin: a gatekeeper for ryanodine receptor function in the myocardium.
The ryanodine receptor (RyR) releases intracellular Ca2+ from the sarcoplasmic reticulum (SR) of beating cardiomyocytes following Ca2+ influx via the voltage-dependent sarcolemmal Ca2+ channel. This crucial cellular event, named ‘Ca2+-induced Ca2+ release’ and discovered three decades ago by Fabiato and Fabiato, is mandatory for the rhythmic contraction as well as for maintaining the force–freq...
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ژورنال
عنوان ژورنال: Journal of Molecular and Cellular Cardiology
سال: 2018
ISSN: 0022-2828
DOI: 10.1016/j.yjmcc.2018.10.011