CaM or cAMP: Linking β-Adrenergic Stimulation to ‘Leaky’ RyRs
CaM or cAMP: Linking β-Adrenergic Stimulation to ‘Leaky’ RyRs
复制标题
DOI：
10.1161/01.res.0000259326.68260.20
复制
发表时间：
2007-02
影响因子：
20.1
通讯作者：
K. Sipido
中科院分区：
文献类型：
--
作者：
K. Sipido
参见相关文章，第391-398页在每次心跳期间，[Ca 2 +]i的瞬时升高将电信号与实际收缩联系起来。从肌浆网（SR）释放的Ca 2+是这种Ca 2+瞬变的主要来源，并通过ryanodine受体RyR发生。RyR是一种Ca 2+激活的通道，主要通过L型Ca 2+通道响应Ca 2+内流，通常称为触发Ca 2+。SR中可用的Ca 2+是SR Ca 2+含量或Ca 2+负载。SR Ca 2+含量在很大程度上取决于由受磷蛋白调节的SERCA向SR中的Ca 2+摄取，以及跨肌膜的Ca 2+通量的平衡。对于后者，Na+/Ca 2+交换器是主要的外排途径，产生内向电流。[Ca 2 +]i处理的改变与心力衰竭中的收缩功能障碍有关，并且涉及几种蛋白质，如SERCA、受磷蛋白和Na+/Ca 2+交换剂，它们都将影响SR中的可用Ca 2+。当Marks等人在2000年报道兰尼碱受体（RyR）的过度磷酸化可能是心力衰竭中异常钙循环的基础时，这是一个新的研究领域的开始，此后引发了许多争论。增加磷酸化被认为导致稳定蛋白FKBP12.6或钙稳定蛋白的结合减少，并导致通道开口增加或“泄漏”RyR。这将导致在兴奋-收缩偶联过程中钙离子的异常释放以及异常门控。胆固醇的异常释放，通过消耗肌浆网，也降低了收缩期Ca 2+水平。同时，舒张压...
See related article, pages 391–398 During each heart beat a transient rise in [Ca2+]i links the electrical signal to the actual contraction. Ca2+ release from the sarcoplasmic reticulum (SR) is the major source of this Ca2+ transient and occurs through the ryanodine receptor, RyR. The RyR is a Ca2+-activated channel, responding to Ca2+ influx, commonly referred to as the trigger Ca2+, predominantly through the L-type Ca2+ channel. The Ca2+ available in the SR is the SR Ca2+ content or Ca2+ load. The SR Ca2+ content depends to a large extent on the Ca2+ uptake into the SR by SERCA, regulated by phospholamban, and also on the balance of Ca2+ fluxes across the sarcolemma. For the latter, the Na+/Ca2+ exchanger is the major efflux pathway, generating an inward current. Alterations in [Ca2+]i handling have been implicated in contractile dysfunction in heart failure, and several proteins are involved such as SERCA, phospholamban and the Na+/Ca2+ exchanger, which would all influence the available Ca2+ in the SR. When Marks et al reported in 2000 that hyperphosphorylation of the ryanodine receptor (RyR) could underlie abnormal calcium cycling in heart failure,1 it was the start of a new area of research that has since sparked a lot of debate. Increased phosphorylation was proposed to lead to reduced binding of the stabilizing protein, FKBP12.6 or calstabin, and result in increased channel openings or ‘leaky’ RyRs. This will lead to abnormal release of Ca2+ in diastole as well as abnormal gating during excitation-contraction coupling. The abnormal release in diastole could, by depleting the sarcoplasmic reticulum, also reduce systolic Ca2+ levels. At the same time, a diastolic …