Chiu Yu-Hsin, Ravichandran Kodi S, Bayliss Douglas A
Department of Pharmacology; University of Virginia; Charlottesville, VA USA.
Beirne B. Carter Center for Immunology Research; University of Virginia; Charlottesville, VA USA; Center for Cell Clearance; University of Virginia; Charlottesville, VA USA; Department of Microbiology; Immunology and Cancer Research; University of Virginia; Charlottesville, VA USA.
Channels (Austin). 2014;8(2):103-9. doi: 10.4161/chan.27545. Epub 2014 Jan 13.
Pannexin 1 (Panx1) channels are generally represented as non-selective, large-pore channels that release ATP. Emerging roles have been described for Panx1 in mediating purinergic signaling in the normal nervous, cardiovascular, and immune systems, where they may be activated by mechanical stress, ionotropic and metabotropic receptor signaling, and via proteolytic cleavage of the Panx1 C-terminus. Panx1 channels are widely expressed in various cell types, and it is now thought that targeting these channels therapeutically may be beneficial in a number of pathophysiological contexts, such as asthma, atherosclerosis, hypertension, and ischemic-induced seizures. Even as interest in Panx1 channels is burgeoning, some of their basic properties, mechanisms of modulation, and proposed functions remain controversial, with recent reports challenging some long-held views regarding Panx1 channels. In this brief review, we summarize some well-established features of Panx1 channels; we then address some current confounding issues surrounding Panx1 channels, especially with respect to intrinsic channel properties, in order to raise awareness of these unsettled issues for future research.
泛素连接蛋白1(Panx1)通道通常被认为是释放ATP的非选择性大孔通道。在正常的神经、心血管和免疫系统中介导嘌呤能信号传导方面,Panx1已被描述了一些新的作用,在这些系统中,它们可能被机械应力、离子型和代谢型受体信号传导以及通过Panx1 C末端的蛋白水解切割激活。Panx1通道在各种细胞类型中广泛表达,现在认为在治疗上靶向这些通道可能在许多病理生理情况下有益,如哮喘、动脉粥样硬化、高血压和缺血性癫痫发作。尽管对Panx1通道的兴趣正在迅速增长,但它们的一些基本特性、调节机制和提出的功能仍存在争议,最近的报告对一些关于Panx1通道的长期观点提出了挑战。在这篇简短的综述中,我们总结了Panx1通道的一些已确立的特征;然后我们讨论了围绕Panx1通道目前一些令人困惑的问题,特别是关于内在通道特性的问题,以便提高对这些未解决问题的认识,供未来研究参考。