Cardiac Mechano-Gated Ion Channels and Arrhythmias.
Cardiac Mechano-Gated Ion Channels and Arrhythmias.
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DOI：
10.1161/circresaha.115.305043
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发表时间：
2016-01-22
影响因子：
20.1
通讯作者：
Kohl P
中科院分区：
文献类型：
--
作者：
Peyronnet R;Nerbonne JM;Kohl P
自生命起源以来，机械力将无处不在，生物体已经进化出感知、解释和响应机械刺激的机制。一般来说，心血管系统，特别是心脏，暴露于不断变化的机械信号，包括拉伸，压缩，弯曲和剪切。心脏调整其性能以适应机械环境，在一系列时间尺度上修改电、机械、代谢和结构特性。许多潜在的调节过程是在心脏内编码的，因此即使在心脏移植受者中也能维持。尽管心脏节律的机械敏感性在医学文献中已经描述了超过世纪，但其分子机制尚未完全了解。由于现代生物物理和分子技术，机械力在心脏生物学中的作用正在被更详细地探索，并且机械转导的详细机制已经开始出现。机械门控离子通道是心脏机械受体。它们引起机械电反馈，被认为有助于正常功能、疾病发展以及潜在的治疗干预。在这篇综述中，我们专注于心脏电生理学的急性机械效应，探索潜在的分子候选人观察到的反应，并讨论其药物调节。由此，我们确定了开放的研究问题，并强调了可能有助于解决这些问题的新兴技术。心脏电生理学受心脏机械环境的严重影响。机械电反馈影响兴奋性，传导和电负荷，仍然是一个被低估的球员在mammogenesis。针对急性机械-电转导的治疗干预的效用是一个值得进一步研究的开放领域。
Mechanical forces will have been omnipresent since the origin of life, and living organisms have evolved mechanisms to sense, interpret and respond to mechanical stimuli. The cardiovascular system in general, and the heart in particular, are exposed to constantly changing mechanical signals, including stretch, compression, bending, and shear. The heart adjusts its performance to the mechanical environment, modifying electrical, mechanical, metabolic, and structural properties over a range of time scales. Many of the underlying regulatory processes are encoded intra-cardially, and are thus maintained even in heart transplant recipients. Although mechano-sensitivity of heart rhythm has been described in the medical literature for over a century, its molecular mechanisms are incompletely understood. Thanks to modern biophysical and molecular technologies, the roles of mechanical forces in cardiac biology are being explored in more detail, and detailed mechanisms of mechano-transduction have started to emerge. Mechano-gated ion channels are cardiac mechano-receptors. They give rise to mechano-electric feedback, thought to contribute to normal function, disease development, and, potentially, therapeutic interventions. In this review, we focus on acute mechanical effects on cardiac electrophysiology, explore molecular candidates underlying observed responses, and discuss their pharmaceutical regulation. From this, we identify open research questions and highlight emerging technologies that may help in addressing them. Cardiac electrophysiology is acutely affected by the heart’s mechanical environment. Mechano-electric feedback affects excitability, conduction, and electrical load, and remains an underestimated player in arrhythmogenesis. The utility of therapeutic interventions targeting acute mechano-electrical transduction is an open field worthy of further study.