Abstract
Heart contraction vitally depends on tightly controlled intracellular Ca regulation. Because contraction is mainly driven by Ca released from the sarcoplasmic reticulum (SR), this organelle plays a particularly important role in Ca regulation. The type two ryanodine receptor (RyR2) is the major SR Ca release channel in ventricular myocytes. Several cardiac pathologies, including myocardial infarction and heart failure, are associated with increased RyR2 activity and diastolic SR Ca leak. It has been suggested that the increased RyR2 activity plays an important role in arrhythmias and contractile dysfunction. Several studies have linked increased SR Ca leak during myocardial infarction and heart failure to the activation of RyR2 in response to oxidative stress. This activation might include direct oxidation of RyR2 as well as indirect activation via phosphorylation or altered interactions with regulatory proteins. Out of ninety cysteine residues per RyR2 subunit, twenty one were reported to be in reduced state that could be potential targets for redox modifications that include S-nitrosylation, S-glutathionylation, and disulfide cross-linking. Despite its clinical significance, molecular mechanisms of RyR dysfunction during oxidative stress are not fully understood. Herein we review the most recent insights into redox-dependent modulation of RyR2 during oxidative stress and heart diseases.
Highlights
Edited by: Laetitia Pereira, Institut National de la Santé et de la Recherche Médicale (INSERM), France
The vast body of evidence demonstrates a direct link between oxidative stress, RyR2 oxidation and increased sarcoplasmic reticulum (SR) Ca leak in several cardiac pathologies, including heart failure (HF) and myocardial infarction (MI)
Effects of oxidative stress on RyR2 may go beyond the direct redox-modification of the channel and can involve dissociation of regulatory proteins and increased phosphorylation by Protein kinase A (PKA) and CaM dependent protein kinase II (CaMKII)
Summary
Ca sparks produces the global Ca transient that initiates contraction. During diastole, cytosolic Ca is pumped back into the SR by the Ca-ATPase (SERCA) and extruded from the cell by the Na-Ca exchanger (NCX) (Bers, 2002). The rate at which SERCA and NCX remove Ca from the cytosol determines how quickly cardiac muscle relaxes to allow the heart to fill with blood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
