Biesiadecki Brandon J, Davis Jonathan P, Ziolo Mark T, Janssen Paul M L
Department of Physiology and Cell Biology and Dorothy M. Davis Heart Lung Institute, College of Medicine, The Ohio State University, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH, 43210-1218, USA.
Biophys Rev. 2014 Dec;6(3-4):273-289. doi: 10.1007/s12551-014-0143-5. Epub 2014 Jul 17.
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.
心肌舒张是心动周期中的一个重要步骤。即使心脏的收缩正常且有力，但舒张期过慢仍会限制心室的正常充盈。人们常常认为舒张仅仅是收缩之后的一个被动过程。然而，几十年来我们对心肌舒张的理解取得了诸多进展，这些进展表明它是一个高度复杂且调控良好的过程。在这篇综述中，我们将讨论三个可能限制心肌舒张速率的不同事件：细胞内钙下降速率、细肌丝失活速率和横桥循环速率。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，使我们对舒张的理解更加复杂。这些过程中的每一个都受到主要心脏生理调节因子将身体氧需求与心输出量相匹配这一需求的持续调节。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下降、细肌丝失活和横桥动力学。我们希望传达我们的结论，即心肌舒张是一个有着复杂制衡机制的过程，不应被视为在单一蛋白质水平上受到调控的单一限速步骤。心肌舒张是一种系统水平的特性，需要细胞内钙下降、细肌丝失活和横桥循环动力学这三个调控系统的基本整合。
