肾脏氯离子通道L-5与Den病的研究进展

Progress of the renal chloride channel CLC-5 and Dent disease

氯离子通道L-5是一种电压依赖性门控通道，其电压门控性不仅受到门控谷氨酸E211、质子谷氨酸E268的调节，还受到赖氨酸K210的影响。在近端肾小管，L-5不仅可以与Meglin蛋白相互作用，共同调节白蛋白的重吸收，还可以影响N’-H’交换体亚型3的活动。LN5基因突变可以导致Den病，近期研究发现了新的L-5致病突变体V505G、L266V和G446等。另外，LN5基因还可以与OLl基因发生双基因突变引起Den病。目前人们对L-5电压门控性的调节机制、生理作用机制及Den病方面仍不完全清楚，该文就此作一综述。

Chloride channel CLC-5 is a voltage-dependent gated channel. The voltage-gated characteristic of CLC-5 is not only regulated by glutamate E211 and E268,but also by lysine K210. In proximal renal tubule, CLC-5 can interact with megalin protein, and adjust the reabsorption of albumin together. CLC-5 can also affect the activities of the sodium hydrogen exchanger isoform 3 in proximal renal tubule. CLCN5 gene mutations can lead to Dent disease,and recent studies have found some new pathogenic mutants of CLC-5, V505G,L266V and G446A,and so on. CLCN5 can also mutate together with ORCL1 ,and then result in Dent disease. However, the regulatory mechanism of the voltage-gated channel, physiological functions and molecular mechanism, and Dent disease are still not entirely clear. In this paper, we will review these problems of CLC-5.