Tri-modal regulation of cardiac muscle relaxation; intracellular calcium decline, thin filament deactivation, and cross-bridge cycling kinetics.
Tri-modal regulation of cardiac muscle relaxation; intracellular calcium decline, thin filament deactivation, and cross-bridge cycling kinetics.
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DOI：
10.1007/s12551-014-0143-5
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发表时间：
2014-12-01
影响因子：
--
通讯作者：
Janssen, Paul M L
中科院分区：
文献类型：
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作者：
Biesiadecki, Brandon J;Davis, Jonathan P;Janssen, Paul M L
心肌松弛是心脏循环的重要步骤。即使心脏的收缩正常有力，过慢的松弛期也会限制心室的正常充盈。放松常常被认为是紧跟着收缩的被动过程。然而，几十年来我们对心肌松弛的理解的进步表明，这是一个高度复杂和调控良好的过程。在这篇综述中，我们将讨论可以限制心肌舒张速率的三个不同的事件：细胞内钙下降的速率，薄丝失活的速率和过桥循环的速率。这些过程中的每一个都直接受到大量分子事件的影响。此外，这三个过程相互作用，使我们对放松的理解进一步复杂化。这些过程中的每一个都是通过主要的心脏生理调节器将身体的氧气需求与心输出量相结合而不断调节的。长度依赖性激活、频率依赖性激活和β -肾上腺素能调节都直接或间接地调节钙的下降、薄丝失活和过桥动力学。我们希望传达我们的结论，即心肌放松是一个复杂的制衡过程，不应被认为是在单一蛋白质水平上调节的单一限速步骤。心肌松弛是一种系统水平的特性，需要三个控制系统的基本整合：细胞内钙下降、细丝失活和过桥循环动力学。
Cardiac muscle relaxation is an essential step in the cardiac cycle. Even when the contraction of the heart is normal and forceful, a relaxation phase that is too slow will limit proper filling of the ventricles. Relaxation is too often thought of as a mere passive process that follows contraction. However, many decades of advancements in our understanding of cardiac muscle relaxation have shown it is a highly complex and well-regulated process. In this review, we will discuss three distinct events that can limit the rate of cardiac muscle relaxation: the rate of intracellular calcium decline, the rate of thin-filament de-activation, and the rate of cross-bridge cycling. Each of these processes are directly impacted by a plethora of molecular events. In addition, these three processes interact with each other, further complicating our understanding of relaxation. Each of these processes is continuously modulated by the need to couple bodily oxygen demand to cardiac output by the major cardiac physiological regulators. Length-dependent activation, frequency-dependent activation, and beta-adrenergic regulation all directly and indirectly modulate calcium decline, thin-filament deactivation, and cross-bridge kinetics. We hope to convey our conclusion that cardiac muscle relaxation is a process of intricate checks and balances, and should not be thought of as a single rate-limiting step that is regulated at a single protein level. Cardiac muscle relaxation is a system level property that requires fundamental integration of three governing systems: intracellular calcium decline, thin filament deactivation, and cross-bridge cycling kinetics.