Articular chondrocytes are embedded in the cartilage of diarthrodial joints and responsible for the synthesis and secretion of extracellular matrix. The extracellular matrix mainly contains collagens and proteoglycans, and covers the articular cartilage to protect from mechanical and biochemical stresses. In mammalian chondrocytes, various types of ion channels have been identified: e.g., voltage-dependent K+ channels, Ca2+-activated K+ channels, ATP-sensitive K+ channels, two-pore domain K+ channels, voltage-dependent Ca2+ channels, store-operated Ca2+ channels, epithelial Na+ channels, acid-sensing ion channels, transient receptor potential channels, and mechanosensitive channels. These channels play important roles for the regulation of resting membrane potential, Ca2+ signaling, pH sensing, mechanotransduction, and cell proliferation in articular chondrocytes. In addition to these cation channels, Cl− channels are known to be expressed in mammalian chondrocytes: e.g., voltage-dependent Cl− channels, cystic fibrosis transmembrane conductance regulator channels, swelling-activated Cl− channels, and Ca2+-activated Cl− channels. Although these chondrocyte Cl− channels are thought to contribute to the regulation of resting membrane potential, Ca2+ signaling, cell volume, cell survival, and endochondral bone formation, the physiological functions have not been fully clarified. Osteoarthritis (OA) is caused by the degradation of articular cartilage, resulting in inflammation and pain in the joints. Therefore the pathophysiological roles of Cl− channels in OA chondrocytes are of considerable interest. Elucidating the physiological and pathological functions of chondrocyte Cl− channels will provide us a more comprehensive understanding of chondrocyte functions and may suggest novel molecular targets of drug development for OA.
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