摘要：
Calcium ion (Ca2+) plays an important role in the heart functionality, which is the linker between electrical activity and mechanical muscle contraction. The sarcoplasmic reticulum (SR) is an important Ca2+ storage compartment inside the cardiac myocyte to maintain low Ca2+ concentration. SR consists of several components: the uptake channel “sarcoATPase (SERCA pump)”, the release channel “ryanodine receptor 2 (RyR2)”, and the Ca2+ buffer inside SR “calsequestrin 2 (CASQ2)”. Lately, a genetic disease caused by mutations of RyR2 and CASQ2 has been found to induce heart arrhythmia named catecholaminergic polymorphic ventricular tachycardia (CPVT) and is a very hot issue. Recently, we have published a mathematical model of the RyR2 mutation and successfully reproduced some key features of CPVT. Furthermore, we have indicated some targets for clinical drug treatments./endoplasmic reticulum Ca2+-
Calcium ion (Ca2+) plays an important role in the heart functionality, which is the linker between electrical activity and mechanical muscle contraction. The sarcoplasmic reticulum (SR) is an important Ca2+ storage compartment inside the cardiac myocyte to maintain low Ca2+ concentration. SR consists of several components: the uptake channel “sarcoATPase (SERCA pump)”, the release channel “ryanodine receptor 2 (RyR2)”, and the Ca2+ buffer inside SR “calsequestrin 2 (CASQ2)”. Lately, a genetic disease caused by mutations of RyR2 and CASQ2 has been found to induce heart arrhythmia named catecholaminergic polymorphic ventricular tachycardia (CPVT) and is a very hot issue. Recently, we have published a mathematical model of the RyR2 mutation and successfully reproduced some key features of CPVT. Furthermore, we have indicated some targets for clinical drug treatments./endoplasmic reticulum Ca2+-
Recent findings pointed out that the class I anti-arrhythmia drug (sodium (Na+) channel blocker) “flecainide” is also a very good candidate for CPVT treatment; however, a controversial issue is about its pharmacological mechanism. One research group claimed that flecainide exerts its effect mainly via the blockade of sodium channel and there is no effect on the SR Ca2+ release channel RyR2. In contrast, another group attributed the effectiveness of flecainide to its blockade on RyR2. We are using our RyR2 mutation model and a newly published subcellular stochastic local control model of SR Ca2+ handling to clarify this controversy and some progress will be reported.