Research and progress on ClC-2

Abstract

Chloride channel 2 (ClC-2) is one of the nine mammalian members of the ClC family. The present review discusses the molecular properties of ClC-2, including CLCN2, ClC-2 promoter and the structural properties of ClC-2 protein; physiological properties; functional properties, including the regulation of cell volume. The effects of ClC-2 on the digestive, respiratory, circulatory, nervous and optical systems are also discussed, in addition to the mechanisms involved in the regulation of ClC-2. The review then discusses the diseases associated with ClC-2, including degeneration of the retina, Sjögren's syndrome, age-related cataracts, degeneration of the testes, azoospermia, lung cancer, constipation, repair of impaired intestinal mucosa barrier, leukemia, cystic fibrosis, leukoencephalopathy, epilepsy and diabetes mellitus. It was concluded that future investigations of ClC-2 are likely to be focused on developing specific drugs, activators and inhibitors regulating the expression of ClC-2 to treat diseases associated with ClC-2. The determination of CLCN2 is required to prevent and treat several diseases associated with ClC-2.

Drosophila ClC‐a is required in glia of the stem cell niche for proper neurogenesis and wiring of neural circuits

“…Among the ion channels expressed in glia, the vertebrate plasma‐membrane ClC‐2 chloride channel has been proposed as one of the channels involved in K + buffering, a key ionic homeostasis process in which glia are involved (Jentsch & Pusch, ; H. Wang et al, ). In the mature nervous system, increased neural activity leads to an increase in extracellular K + , which can alter neuronal excitability.…”

“…Among the ion channels expressed in glia, the vertebrate plasmamembrane ClC-2 chloride channel has been proposed as one of the channels involved in K + buffering, a key ionic homeostasis process in which glia are involved (Jentsch & Pusch, 2018;H. Wang et al, 2017).…”

Lack of ClC-2 Alleviates High Fat Diet-Induced Insulin Resistance and Non-Alcoholic Fatty Liver Disease

“…ClC-2, a member of ClCs family, is almost ubiquitously expressed, including in the liver [12, 13]. Recently, ClC-2 attracted increasing attention because ClC-2 has been implicated in several diseases, such as cystic fibrosis, leukemia and diabetes mellitus [12, 14]. Importantly, fatty acids can activate human ClC-2 Cl- channel [15], further supports the involvement in metabolic disorders.…”

“…Chloride channels (ClCs) function as a kind of permeable channel or protein, which are encoded and regulated by the genes of ClC family [12]. ClC-2, a member of ClCs family, is almost ubiquitously expressed, including in the liver [12, 13]. Recently, ClC-2 attracted increasing attention because ClC-2 has been implicated in several diseases, such as cystic fibrosis, leukemia and diabetes mellitus [12, 14].…”

“…Increasing lines of evidences have suggested that dysregulated intracellular Cl- level is associated with vascular inflammation, hypertension, lipid accumulation and atherosclerosis [9-11]. Chloride channels (ClCs) function as a kind of permeable channel or protein, which are encoded and regulated by the genes of ClC family [12]. ClC-2, a member of ClCs family, is almost ubiquitously expressed, including in the liver [12, 13].…”