Lang Di, Glukhov Alexey V
Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health.
Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health;
J Vis Exp. 2016 Dec 2(118):54773. doi: 10.3791/54773.
Sino-atrial node (SAN) dysfunctions and associated complications constitute important causes of morbidity in patients with cardiac diseases. The development of novel pharmacological therapies to cure these patients relies on the thorough understanding of both normal physiology and pathophysiology of the SAN. Among the studies of cardiac pacemaking, the mouse SAN is widely used due to its feasibility for modifications in the expression of different genes that encode SAN ion channels or calcium handling proteins. Emerging evidence from electrophysiological and histological studies has also proved the representativeness and similarity of the mouse SAN structure and functions to larger mammals, including the presence of specialized conduction pathways from the SAN to the atrium and a complex pacemakers' hierarchy within the SAN. Recently, the technique of optical mapping has greatly facilitated the exploration and investigation of the origin of excitation and conduction within and from the mouse SAN, which in turn has extended the understanding of the SAN and benefited clinical treatments of SAN dysfunction associated diseases. In this manuscript, we have described in detail how to perform the optical mapping of the mouse SAN from the intact, Langendorff-perfused heart and from the isolated atrial preparation. This protocol is a useful tool to enhance the understanding of mouse SAN physiology and pathophysiology.
窦房结(SAN)功能障碍及相关并发症是心脏病患者发病的重要原因。开发新型药物疗法来治疗这些患者依赖于对窦房结正常生理和病理生理的透彻理解。在心脏起搏研究中,小鼠窦房结因其可对编码窦房结离子通道或钙处理蛋白的不同基因表达进行修饰而被广泛使用。电生理和组织学研究的新证据也证明了小鼠窦房结结构和功能与大型哺乳动物的代表性和相似性,包括存在从窦房结到心房的特殊传导通路以及窦房结内复杂的起搏层次结构。最近,光学映射技术极大地促进了对小鼠窦房结内部及从窦房结发出的兴奋和传导起源的探索和研究,这反过来又扩展了对窦房结的理解,并有益于窦房结功能障碍相关疾病的临床治疗。在本手稿中,我们详细描述了如何从完整的、Langendorff灌注心脏以及分离的心房标本中对小鼠窦房结进行光学映射。该方案是增进对小鼠窦房结生理和病理生理理解的有用工具。