Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, 03722, South Korea.
The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, 03722, South Korea.
Pflugers Arch. 2020 Aug;472(8):1003-1018. doi: 10.1007/s00424-020-02425-x. Epub 2020 Jul 4.
Many anion channels, frequently referred as Cl channels, are permeable to different anions in addition to Cl. As the second-most abundant anion in the human body, HCO permeation via anion channels has many important physiological roles. In addition to its classical role as an intracellular pH regulator, HCO also controls the activity and stability of dissolved proteins in bodily fluids such as saliva, pancreatic juice, intestinal fluid, and airway surface liquid. Moreover, HCO permeation through these channels affects membrane potentials that are the driving forces for transmembrane transport of solutes and water in epithelia and affect neuronal excitability in nervous tissue. Consequently, aberrant HCO transport via anion channels causes a number of human diseases in respiratory, gastrointestinal, genitourinary, and neuronal systems. Notably, recent studies have shown that the HCO permeabilities of several anion channels are not fixed and can be altered by cellular stimuli, findings which may have both physiological and pathophysiological significance. In this review, we summarize recent progress in understanding the molecular mechanisms and the physiological roles of HCO permeation through anion channels. We hope that the present discussions can stimulate further research into this very important topic, which will provide the basis for human disorders associated with aberrant HCO transport.
许多阴离子通道，通常被称为 Cl 通道，除了 Cl 之外，还对其他阴离子具有通透性。HCO 通过阴离子通道的渗透是人体中第二丰富的阴离子，具有许多重要的生理作用。除了作为细胞内 pH 调节剂的经典作用外，HCO 还控制着唾液、胰液、肠液和气道表面液等体液中溶解蛋白的活性和稳定性。此外，这些通道中 HCO 的渗透会影响膜电位，而膜电位是上皮细胞中溶质和水跨膜运输的驱动力，并影响神经组织中神经元的兴奋性。因此，阴离子通道中异常的 HCO 转运导致呼吸、胃肠道、泌尿生殖和神经元系统中的多种人类疾病。值得注意的是，最近的研究表明，几种阴离子通道的 HCO 通透性不是固定的，可被细胞刺激改变，这些发现可能具有生理和病理生理意义。在这篇综述中，我们总结了近年来对 HCO 通过阴离子通道渗透的分子机制和生理作用的理解进展。我们希望目前的讨论能激发对这一非常重要课题的进一步研究，为与异常 HCO 转运相关的人类疾病提供基础。
