PDF(Pubmed)
Abstract：
Inwardly rectifying potassium (Kir) channels are broadly expressed in many mammalian organ systems, where they contribute to critical physiological functions. However, the importance and function of the Kir5.1 channel (encoded by the KCNJ16 gene) have not been fully recognized. This review focuses on the recent advances in understanding the expression patterns and functional roles of Kir5.1 channels in fundamental physiological systems vital to potassium homeostasis and neurological disorders. Recent studies have described the role of Kir5.1-forming Kir channels in mouse and rat lines with mutations in the Kcnj16 gene. The animal research reveals distinct renal and neurological phenotypes, including pH and electrolyte imbalances, blunted ventilatory responses to hypercapnia/hypoxia, and seizure disorders. Furthermore, it was confirmed that these phenotypes are reminiscent of those in patient cohorts in which mutations in the KCNJ16 gene have also been identified, further suggesting a critical role for Kir5.1 channels in homeostatic/neural systems health and disease. Future studies that focus on the many functional roles of these channels, expanded genetic screening in human patients, and the development of selective small-molecule inhibitors for Kir5.1 channels, will continue to increase our understanding of this unique Kir channel family member.
摘要：
内向整流钾（Kir）通道在许多哺乳动物器官系统中广泛表达，它们有助于关键的生理功能。然而,Kir5.1通道(由KCNJ16基因编码)的重要性和功能尚未得到充分认识.这篇综述的重点是在了解Kir5.1通道在对钾稳态和神经系统疾病至关重要的基本生理系统中的表达模式和功能作用方面的最新进展。最近的研究已经描述了Kir5.1形成Kir通道在Kcnj16基因突变的小鼠和大鼠品系中的作用。动物研究揭示了不同的肾脏和神经表型，包括pH和电解质失衡，对高碳酸血症/缺氧的通气反应减弱，和癫痫症。此外，已证实，这些表型让人想起那些在KCNJ16基因突变的患者队列中，进一步表明Kir5.1通道在稳态/神经系统健康和疾病中的关键作用。未来的研究集中在这些渠道的许多功能作用，扩大对人类患者的基因筛查，以及Kir5.1通道的选择性小分子抑制剂的开发，将继续增加我们对这个独特的Kir频道家族成员的了解。
