MacDonald Eilidh A, Stoyek Matthew R, Rose Robert A, Quinn T Alexander
Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada.
Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada.
Prog Biophys Mol Biol. 2017 Nov;130(Pt B):198-211. doi: 10.1016/j.pbiomolbio.2017.07.012. Epub 2017 Jul 22.
Excitation of the heart occurs in a specialised region known as the sinoatrial node (SAN). Tight regulation of SAN function is essential for the maintenance of normal heart rhythm and the response to (patho-)physiological changes. The SAN is regulated by extrinsic (central nervous system) and intrinsic (neurons, peptides, mechanics) factors. The positive chronotropic response to stretch in particular is essential for beat-by-beat adaptation to changes in hemodynamic load. Yet, the mechanism of this stretch response is unknown, due in part to the lack of an appropriate experimental model for targeted investigations. We have been investigating the zebrafish as a model for the study of intrinsic regulation of SAN function. In this paper, we first briefly review current knowledge of the principal components of extrinsic and intrinsic SAN regulation, derived primarily from experiments in mammals, followed by a description of the zebrafish as a novel experimental model for studies of intrinsic SAN regulation. This mini-review is followed by an original investigation of the response of the zebrafish isolated SAN to controlled stretch. Stretch causes an immediate and continuous increase in beating rate in the zebrafish isolated SAN. This increase reaches a maximum part way through a period of sustained stretch, with the total change dependent on the magnitude and direction of stretch. This is comparable to what occurs in isolated SAN from most mammals (including human), suggesting that the zebrafish is a novel experimental model for the study of mechanisms involved in the intrinsic regulation of SAN function by mechanical effects.
心脏的兴奋发生在一个被称为窦房结（SAN）的特殊区域。严格调节窦房结功能对于维持正常心律以及对（病理-）生理变化的反应至关重要。窦房结受外在（中枢神经系统）和内在（神经元、肽、力学）因素调节。特别是对拉伸的正性变时反应对于逐搏适应血流动力学负荷变化至关重要。然而，这种拉伸反应的机制尚不清楚，部分原因是缺乏用于靶向研究的合适实验模型。我们一直在研究斑马鱼作为研究窦房结功能内在调节的模型。在本文中，我们首先简要回顾主要从哺乳动物实验中获得的关于窦房结外在和内在调节主要成分的现有知识，然后描述斑马鱼作为研究窦房结内在调节的新型实验模型。在这篇小型综述之后是对斑马鱼分离的窦房结对受控拉伸反应的原创性研究。拉伸导致斑马鱼分离的窦房结的搏动率立即持续增加。这种增加在持续拉伸一段时间后达到最大值，总变化取决于拉伸的幅度和方向。这与大多数哺乳动物（包括人类）分离的窦房结中发生的情况相当，表明斑马鱼是研究机械效应参与窦房结功能内在调节机制的新型实验模型。
