Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; HCR (Heidelberg Center for Heart Rhythm Disorders), University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Department of Pediatric Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany; Centre for Organismal Studies, Heidelberg University, Im Neuenheimer Feld 230, 69120 Heidelberg, Germany; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany; Molecular Medicine Partnership Unit, EMBL and Heidelberg University, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany.
Eur J Pharmacol. 2018 Jul 15;831:94-102. doi: 10.1016/j.ejphar.2018.05.007. Epub 2018 May 9.
Human K17.1 (TASK-4, TALK-2) two-pore-domain potassium (K) channels have recently been implicated in heart rhythm disorders including atrial fibrillation and conduction disease. The functional in vivo significance of K17.1 currents in cardiac electrophysiology remains incompletely understood. Danio rerio (zebrafish) may be utilized to elucidate the role of cardiac K channels in vivo. The aim of this work was to identify and characterize the zebrafish ortholog of K17.1 in comparison to its human counterpart. The zkcnk17 coding sequence was amplified from zebrafish cDNA. Zebrafish kcnk17 mRNA expression was assessed by polymerase chain reaction. Human and zebrafish K17.1 currents were analyzed using two-electrode voltage clamp electrophysiology and the Xenopus oocyte expression system. Kcnk17 mRNA was detected in zebrafish brain. Human and zebrafish K17.1 proteins exhibited 33.4% identity. Zebrafish K17.1 channels conducted K selective currents with open rectification properties. Both human and zebrafish K17.1 were inhibited by barium. In contrast to human K17.1, zK17.1 currents were not sensitive to extracellular alkalization, likely due to the lack of a lysine residue involved in pH sensing of hK17.1. In conclusion, zebrafish and human K17.1 channels display similar structural and regulatory properties. Zebrafish may serve as an in vivo model to study neuronal K17.1 function but does not appear appropriate for cardiac electrophysiology studies. Differences in pH sensitivity of zK17.1 currents need to be considered when zebrafish data are extrapolated to human physiology.
人类 K17.1（TASK-4，TALK-2）双孔域钾（K）通道最近被牵连到心律失常，包括心房颤动和传导疾病。K17.1 电流在心脏电生理学中的功能的体内意义仍然不完全理解。斑马鱼（斑马鱼）可能被用来阐明心脏 K 通道在体内的作用。这项工作的目的是鉴定和描述 K17.1 在斑马鱼中的同源物，并将其与人类相对比。zkcnk17 编码序列从斑马鱼 cDNA 中扩增。通过聚合酶链反应评估斑马鱼 kcnk17 mRNA 的表达。使用双电极电压钳电生理学和非洲爪蟾卵母细胞表达系统分析人类和斑马鱼 K17.1 电流。在斑马鱼大脑中检测到 kcnk17 mRNA。人类和斑马鱼 K17.1 蛋白显示出 33.4%的同一性。斑马鱼 K17.1 通道传导 K 选择性电流，具有开放整流特性。人类和斑马鱼 K17.1 均被钡抑制。与人类 K17.1 不同，zK17.1 电流对细胞外碱化不敏感，这可能是由于缺乏参与 hK17.1 pH 感应的赖氨酸残基。总之，斑马鱼和人类 K17.1 通道显示出相似的结构和调节特性。斑马鱼可以作为研究神经元 K17.1 功能的体内模型，但不适用于心脏电生理学研究。当将斑马鱼数据推断到人类生理学时，需要考虑 zK17.1 电流 pH 敏感性的差异。
