KCNK2 is a 2 pore domain potassium channel involved in maintaining cellular membrane resting potentials. Although KCNK2 is regarded as a mechanosensitive ion channel, it can also be gated chemically. Previous research indicates that KCNK2 expression is particularly enriched in neuronal and cardiac tissues. In this respect, KCNK2 plays an important role in neuroprotection and has also been linked to cardiac arrhythmias. KCNK2 has subsequently become an attractive pharmacologic target for developing preventative/curative strategies for neuro/cardio pathophysiological conditions. Zebrafish represent an important in vivo model for rapidly analysing pharmacological compounds. We therefore sought to identify and characterise zebrafish kcnk2 to allow this model system to be incorporated into therapeutic research. Our data indicates that zebrafish possess two kcnk2 orthologs, kcnk2a and kcnk2b. Electrophysiological analysis of both zebrafish Kcnk2 orthologs shows that, like their human counterparts, they are activated by different physiological stimuli such as mechanical stretch, polyunsaturated fatty acids and intracellular acidification. Furthermore, both zebrafish Kcnk2 channels are inhibited by the human KCNK2 inhibitory peptide spadin. Taken together, our results demonstrate that both Kcnk2a and Kcnk2b share similar biophysiological and pharmacological properties to human KCNK2 and indicate that the zebrafish will be a useful model for developing KCNK2 targeting strategies.

中文翻译：

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鉴定和表征两个与斑马鱼Twik相关的钾通道Kcnk2a和Kcnk2b。

KCNK2是一个2孔结构域钾通道，参与维持细胞膜的静息电位。尽管KCNK2被认为是机械敏感的离子通道，但它也可以在化学上进行门控。先前的研究表明，KCNK2表达在神经元和心脏组织中特别丰富。在这方面，KCNK2在神经保护中起重要作用，并且还与心律不齐相关。KCNK2随后已成为开发针对神经/心脏病理生理状况的预防/治疗策略的引人注目的药理学靶标。斑马鱼代表了一种重要的体内模型，用于快速分析药理化合物。因此，我们寻求鉴定和表征斑马鱼kcnk2，以使该模型系统可以纳入治疗研究。我们的数据表明斑马鱼拥有两个kcnk2直系同源物kcnk2a和kcnk2b。对两种斑马鱼Kcnk2直系同源物的电生理分析表明，与人类的斑马鱼Kcnk2直系同源物一样，它们被不同的生理刺激（例如机械拉伸，多不饱和脂肪酸和细胞内酸化）激活。此外，两个斑马鱼的Kcnk2通道均被人KCNK2抑制肽spadin抑制。两者合计，我们的结果表明Kcnk2a和Kcnk2b都具有与人类KCNK2相似的生物生理和药理特性，并表明斑马鱼将成为发展KCNK2靶向策略的有用模型。它们被不同的生理刺激例如机械拉伸，多不饱和脂肪酸和细胞内酸化激活。此外，两个斑马鱼的Kcnk2通道均被人KCNK2抑制肽spadin抑制。两者合计，我们的结果表明Kcnk2a和Kcnk2b都具有与人类KCNK2相似的生物生理和药理特性，并表明斑马鱼将成为发展KCNK2靶向策略的有用模型。它们被不同的生理刺激例如机械拉伸，多不饱和脂肪酸和细胞内酸化激活。此外，两个斑马鱼的Kcnk2通道均被人KCNK2抑制肽spadin抑制。两者合计，我们的结果表明Kcnk2a和Kcnk2b都具有与人类KCNK2相似的生物生理和药理特性，并表明斑马鱼将成为发展KCNK2靶向策略的有用模型。