铁死亡介导K_(ATP)通道功能受损致心力衰竭机制的研究进展

Dysfunctional Mechanism of K_(ATP)Channel in Heart Failure Induced by Ferroptosis

心力衰竭是一种以临床预后差、死亡率高为主要特点的心血管疾病。K_(ATP)通道偶联能量代谢与细胞膜兴奋性,在可兴奋细胞中起着关键调控作用。K_(ATP)通道激活使膜电位超极化,减少早期后除极介导心律失常的发生。心肌细胞K_(ATP)通道在生理条件下活性较低,而在严重缺血和长时间缺氧导致腺苷三磷酸/腺苷二磷酸比值降低时激活,降低细胞兴奋性,从而阻止动作电位的产生和细胞收缩。铁死亡是一种新型细胞程序性死亡方式,其特征在于Fe^(2+)和脂质过氧化物代谢异常导致的膜系统中脂质过氧化物的致死性积累,研究发现铁死亡可能对K_(ATP)通道的功能造成损伤,恶化心脏功能。因此,现就铁死亡介导K_(ATP)通道功能受损在心力衰竭中调控机制进行综述。

Heart failure is a global cardiovascular disease characterized by poor clinical prognosis and high mortality.K_(ATP)channel play pivotal roles in excitable cells and link cellular metabolism with membrane excitability.The action potential converts electricity into dynamics by ion channels mediated ion-exchange generate the systole,which composes every single heartbeat.Activation of the K_(ATP)channel repolarizes the membrane potential and decreases the occurrence of early after-depolarization-mediated arrhythmias.Cardiac K_(ATP)channel have less function under physiological conditions and open during severe and prolonged anoxia due to reduced adenosine triphosphate/adenosine diphosphate ratio,lessening cellular excitability,thus preventing action potential generation and cell contraction.Accumulated evidence indicated that ferroptosis may cause damage to the K_(ATP)channel.Hence,we describe the potential damage role of ferroptosis in the K_(ATP)channel,lucubrating the potential mechanisms and insight into the clinical therapeutic strategy.