Identification and functional characterization of zebrafish K_2P17.1 (TASK-4, TALK-2) two-pore-domain K⁺ channels

Human K_2P17.1 (TASK-4, TALK-2) two-pore-domain potassium (K_2P) channels have recently been implicated in heart rhythm disorders including atrial fibrillation and conduction disease. The functional in vivo significance of K_2P17.1 currents in cardiac electrophysiology remains incompletely understood. Danio rerio (zebrafish) may be utilized to elucidate the role of cardiac K_2P channels in vivo. The aim of this work was to identify and characterize the zebrafish ortholog of K_2P17.1 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 K_2P17.1 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 K_2P17.1 proteins exhibited 33.4% identity. Zebrafish K_2P17.1 channels conducted K⁺ selective currents with open rectification properties. Both human and zebrafish K_2P17.1 were inhibited by barium. In contrast to human K_2P17.1, zK_2P17.1 currents were not sensitive to extracellular alkalization, likely due to the lack of a lysine residue involved in pH sensing of hK_2P17.1. In conclusion, zebrafish and human K_2P17.1 channels display similar structural and regulatory properties. Zebrafish may serve as an in vivo model to study neuronal K_2P17.1 function but does not appear appropriate for cardiac electrophysiology studies. Differences in pH sensitivity of zK_2P17.1 currents need to be considered when zebrafish data are extrapolated to human physiology.