Acid- and Volume-Sensitive Chloride Currents in Human Chondrocytes.

摘要: Chondrocytes face extreme alterations of extracellular osmolarity and pH, which force them to appropriately regulate their cell volume (CV) cellular pH. Perturbations these mechanisms lead chondrocyte death ultimately osteoarthritis (OA), the most common chronic joint diseases worldwide. OA hallmarks are altered cartilage hydration severe fluid acidification. Impaired CV regulation acidotoxicity contribute disease progression volume-sensitive anion channels upregulated in OA. This study assessed effect hypotonicity acidification on Cl- conductances regulation. currents membrane potentials were measured human C28/I2 cells primary chondrocytes using patch clamp technique. Intracellular pH was by BCECF fluorescence, measurements performed Coulter method, viability/cell a resazurin assay. Hypotonic swelling caused activation outwardly rectifying (VSOR) current followed regulatory decrease (RVD), attenuated channel blocker DCPIB. Extracellular, but not intracellular ≤ 5.0 elicited an acid-sensitive (ASOR) conductance. Activation either depolarized potential. Under simultaneous hypotonic acidic stimulation, VSOR ASOR transiently coactivated, giving rise mixed phenotype. Over time gradually vanished residual conductance showed pure Extracellular isotonic gain complete suppression RVD under conditions. The results suggest that deactivation conditions impairs chondrocytes, is likely compromise viability.