Institute of Functional Genomics, University of Montpellier, CNRS, INSERM, LabEx ICST, 34094 Montpellier, France.
Neuromyogene Institut, Claude Bernard University, Lyon 1, 69008 Villeurbanne, France.
Int J Mol Sci. 2023 Apr 4;24(7):6720. doi: 10.3390/ijms24076720.
The rhythmical nature of the cardiovascular system constantly generates dynamic mechanical forces. At the centre of this system is the heart, which must detect these changes and adjust its performance accordingly. Mechanoelectric feedback provides a rapid mechanism for detecting even subtle changes in the mechanical environment and transducing these signals into electrical responses, which can adjust a variety of cardiac parameters such as heart rate and contractility. However, pathological conditions can disrupt this intricate mechanosensory system and manifest as potentially life-threatening cardiac arrhythmias. Mechanosensitive ion channels are thought to be the main proponents of mechanoelectric feedback as they provide a rapid response to mechanical stimulation and can directly affect cardiac electrical activity. Here, we demonstrate that the mechanosensitive ion channel is expressed in zebrafish cardiomyocytes. Furthermore, chemically prolonging activation in zebrafish results in cardiac arrhythmias. indicating that this ion channel plays an important role in mechanoelectric feedback. This also raises the possibility that gain of function mutations could be linked to heritable cardiac arrhythmias in humans.
心血管系统的节奏性本质使其持续产生动态机械力。在这个系统的中心是心脏，它必须检测到这些变化，并相应地调整其性能。机电反馈提供了一种快速的机制，可以检测机械环境中的微小变化，并将这些信号转化为电响应，从而调整各种心脏参数，如心率和收缩性。然而，病理条件可能会破坏这个复杂的机械感觉系统，并表现为潜在的危及生命的心律失常。机械敏感离子通道被认为是机电反馈的主要支持者，因为它们对机械刺激有快速的反应，并且可以直接影响心脏的电活动。在这里，我们证明机械敏感离子通道 在斑马鱼心肌细胞中表达。此外，在斑马鱼中化学延长 的激活导致心律失常。表明该离子通道在机电反馈中起重要作用。这也提出了这样一种可能性，即功能获得性突变可能与人类遗传性心律失常有关。
