25 June 2010
Med Sci Monit 2010; 16(7): HY23-26 :: ID: 880912
We propose that stabilizing ryanodine receptor type 2 (RyR2) may be a novel strategy for the treatment of atrial fibrillation (AF). Sarcoplasmic reticulum (SR) dysfunction caused by hyperphosphorylation of RyR2 and/or partial depletion of the stabilizing subunit calstabin2 has been indicated in AF. RyR2 stabilization may prevent SR dysfunction and thereby protect the heart from damage. Hypertrophy, hyperthyroidism and heart failure, three common pathological conditions associated with AF, result in increased SR Ca2+ leak via RyR2. RyR2 stabilization may prevent SR Ca2+ leak and thereby prevent AF. Triggered activity appears to underlie atrial ectopic foci, which cause AF. Diastolic Ca2+ leak from SR via RyR2 may initiate triggered activity. Therefore, modulating RyR2 opening probability would be predicted to protect against triggered activity. Atrial oxidative stress plays a contributing role in the pathogenesis of AF. RyR2 is a target of reactive oxygen species, and chronic RyR2 oxidation increases RyR2 opening probability in a more sustained, less reversible manner. Strategies that attenuate oxidative stress and protect against AF may also contribute to RyR2 stabilization. Finally, KN-3 and JTV519, two compounds that stabilize RyR2 in the closed state, prevent the induction of triggered activity and suppress the inducibility of sustained AF. Thus, it is reasonable to speculate that experimental approaches designed to improve RyR2 stabilization will drive a novel conceptual revolution in AF drug development and lead to new clinical investigations.
Keywords: Models, Cardiovascular, Ryanodine Receptor Calcium Release Channel - metabolism, Atrial Fibrillation - therapy
Most Viewed Current Articles
13 Apr 2020 : Original articleOutcome of 24 Weeks of Combined Schroth and Pilates Exercises on Cobb Angle, Angle of Trunk Rotation, Chest...
Med Sci Monit Basic Res 2020; 26:e920449
11 May 2020 : Original articleAnalysis of Psychological and Sleep Status and Exercise Rehabilitation of Front-Line Clinical Staff in the ...
Med Sci Monit Basic Res 2020; 26:e924085
05 Jan 2021 : Review articleA Southeast Asian Perspective on the COVID-19 Pandemic: Hemoglobin E (HbE)-Trait Confers Resistance Against...
Med Sci Monit Basic Res 2021; 27:e929207
10 Aug 2020 : Clinical ResearchEffects of Cognitive Task Training on Dynamic Balance and Gait of Patients with Stroke: A Preliminary Rando...
Med Sci Monit Basic Res 2020; 26:e925264