Correction of the defective inter-domain interaction of cardiac ryanodine receptor prevents catecholaminergic polymorphic ventricular tachycardia

儿茶酚胺能多形性室性心动过速(CPVT)是由心脏兰尼定受体(RyR2)区域发生单点突变引起的。CPVT突变导致RyR2区域间相互作用缺陷，从而降低了通道激活的鲁米那[Ca~(2+)]阈值，使其对蛋白激酶A依赖的磷酸化反应敏感，进而导致CPVT。在人CPVT相关的RyR2^；R2474S/&gt；敲入(Ki)小鼠模型中，CPVT可能能够通过纠正RyR2有缺陷的域间相互作用和抑制钙泄漏来预防。

Catecholaminergic polymorphic ventricular tachycardia(CPVT )is known to be caused by single point mutation taking place in well defined regions of the cardiac ryanodine receptor (RyR2). CPVT mutation causes defective interdomain interaction of RyR2, which reduces the threshold of luminal [Ca2+] for channel activation, sensitizes to the protein kinase A- dependent phosphorylation, and in turn leads to CPVT. In a human CPVT-associated RyR2^<R2474S/+> knock-in (KI) mouse model, CPVT might be able to be prevented by correcting the defective inter-domain interaction of RyR2 and inhibiting Ca2+ leak.