摘要
FKBP12.6从RyR2解离导致通道构象及功能改变。Ca2+从SR漏出使SR的Ca2+负荷减少,Ca2+瞬变减少,舒缩时RyR2耦联障碍,最终引起心肌功能异常。而且RyR2对CICR敏感性提高导致心肌迟后去极诱发心律失常。通过过表达或增加FKBP12.6对RyR2亲和力可以改善通道缺陷,从而使心脏功能及心律失常得到改善。
The dissociation of FKBP12.6 from RyR2 in SR of cardiac myocytes causes conformational and functional changes of the channel and an abnormal Ca^2＋ leak from SR during diastole. These changes decrease Ca^2＋ load in SR, Ca^2＋ transient during systole and uncouples multiple RyR2s, which subsequently lead to dysfunction of systole and diastole. The increase of RyR2 sensitivity to CICR results is delayed after depolarization and triggers fatal ventricular arrhythmia and sudden death. By overexpressing FKBP12.6 or enhancing the affinity of FKBP12.6 to RyR2, it can correct the defect of RyR2 and thus improve cardiac function and prevent from arrhythmia. Therefore the restoration of normal association between FKBP12.6 and RyR2 can served as a new focus of therapy.
出处
《心血管病学进展》
CAS
2007年第6期979-982,共4页
Advances in Cardiovascular Diseases
基金
国家自然科学基金资助项目(30371363)
