Abstract
Acid-sensing ion channels (ASICs) are cationic channels that are activated by extracellular acidification and implicated in pain perception, ischemic stroke, mechanosensation, learning, and memory. It has been shown that ASIC1a is an extracellular pH sensor in the central and peripheral nervous systems, but its physiological and pathological roles in non-neural cells are poorly understood. We demonstrated a novel physiological function of ASIC1a in rat articular chondrocytes. The expression of ASIC1a mRNA and protein in rat articular chondrocytes was evaluated by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. The distribution of ASIC1a protein located in articular chondrocytes was determined by using immunofluorescence cell staining. The possible molecular mechanisms of articular chondrocytes pH sensing, as assessed by recording intracellular calcium ([Ca2+]i) in chondrocytes, were analyzed by using the laser scanning confocal microscopy technique. The cell injure following acid exposure was analyzed with lactate dehydrogenase release assay and electron microscopy. mRNA and protein expression showed that ASIC1a was expressed abundantly in these cells. In cultured chondrocytes, extracellular pH 6.0 increased intracellular calcium in the presence of extracellular Ca2+. The ASIC1a-specific blocker PcTX venom significantly reduced this increase in [Ca2+]i, and inhibited acid-induced articular chondrocyte injury. However, the increase in [Ca2+]i and articular chondrocyte injury were not observed in the absence of extracellular Ca2+. These findings show that increased [Ca2+]i, mediated via ASIC1a, might contribute to acidosis-induced articular chondrocyte injury.
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This study was supported by the China National Science Foundation grants No. 30901526 and No. 30873080.
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Yuan, FL., Chen, FH., Lu, WG. et al. Acid-sensing ion channel 1a mediates acid-induced increases in intracellular calcium in rat articular chondrocytes. Mol Cell Biochem 340, 153–159 (2010). https://doi.org/10.1007/s11010-010-0412-y
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DOI: https://doi.org/10.1007/s11010-010-0412-y