Chung Jae-Hoon, Biesiadecki Brandon J, Ziolo Mark T, Davis Jonathan P, Janssen Paul M L
Department of Physiology and Cell Biology, The Ohio State University Wexner Medical CenterColumbus, OH, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterColumbus, OH, USA; Medical Scientist Training Program and Biomedical Sciences Graduate Program, The Ohio State University Wexner Medical CenterColumbus, OH, USA.
Department of Physiology and Cell Biology, The Ohio State University Wexner Medical CenterColumbus, OH, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterColumbus, OH, USA.
Front Physiol. 2016 Dec 16;7:562. doi: 10.3389/fphys.2016.00562. eCollection 2016.
Myofilament calcium sensitivity is an often-used indicator of cardiac muscle function, often assessed in disease states such as hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). While assessment of calcium sensitivity provides important insights into the mechanical force-generating capability of a muscle at steady-state, the dynamic behavior of the muscle cannot be sufficiently assessed with a force-pCa curve alone. The equilibrium dissociation constant (K) of the force-pCa curve depends on the ratio of the apparent calcium association rate constant (k) and apparent calcium dissociation rate constant (k) of calcium on TnC and as a stand-alone parameter cannot provide an accurate description of the dynamic contraction and relaxation behavior without the additional quantification of k or k, or actually measuring dynamic twitch kinetic parameters in an intact muscle. In this review, we examine the effect of length, frequency, and beta-adrenergic stimulation on myofilament calcium sensitivity and dynamic contraction in the myocardium, the effect of membrane permeabilization/mechanical- or chemical skinning on calcium sensitivity, and the dynamic consequences of various myofilament protein mutations with potential implications in contractile and relaxation behavior.
肌丝钙敏感性是常用的心肌功能指标,常用于评估肥厚型心肌病(HCM)和扩张型心肌病(DCM)等疾病状态。虽然钙敏感性评估能为肌肉在稳态下产生机械力的能力提供重要见解,但仅通过力 - pCa曲线无法充分评估肌肉的动态行为。力 - pCa曲线的平衡解离常数(K)取决于钙在肌钙蛋白C(TnC)上的表观钙结合速率常数(k)和表观钙解离速率常数(k)的比值,作为一个独立参数,如果不额外量化k或k,或者不在完整肌肉中实际测量动态抽搐动力学参数,就无法准确描述动态收缩和舒张行为。在本综述中,我们研究了长度、频率和β - 肾上腺素能刺激对心肌肌丝钙敏感性和动态收缩的影响,膜通透性/机械或化学去皮对钙敏感性的影响,以及各种肌丝蛋白突变对收缩和舒张行为潜在影响的动态后果。