Abstract
Articular chondrocytes play an important role in the formation of the cartilage in synovial joints, which is closely influenced by mechanical or osmotic stress. In the present study, whole-cell membrane currents were recorded from isolated rabbit articular chondrocytes during exposure to hyposmotic external solution, under conditions where Na+, Ca2+ and K+ channels and electrogenic transporters were minimized. Articular chondrocytes responded to a hyposmotic external solution (Na+ reduction to about 70% of control) with an osmotic cell swelling, which was consistently accompanied by the activation of an outwardly-rectifying Cl− current (swelling-activated Cl− current, ICl,swell). ICl,swell was practically time-independent at potentials negative to +30 mV but exhibited a gradual inactivation at more positive potentials. Bath application of arachidonic acid (AA) reversibly and concentration-dependently blocked ICl,swell with an IC50 of 0.58 μM and Hill coefficient of 1.9. The maximal effect (100% block) was obtained with 10 μM AA. Neither cyclooxygenase inhibitor indomethacin (10 μM) nor lipoxygenase inhibitor nordihydroguaretic acid (NDGA, 3 μM) significantly affected the inhibitory action of AA. In addition, PGE2, LTB4 and LTD4 did not have any appreciable effect on ICl,swell, suggesting that AA directly affected ICl,swell. The present study thus confirms the presence of ICl,swell which exhibits a high sensitivity to inhibition by AA in rabbit articular chondrocytes. [J Physiol Sci. 2006;56 Suppl:S159]
