The metabolic activity of articular chondrocytes is influenced by osmotic alterations that occur in articular cartilage secondary to mechanical load. The mechanisms that sense and transduce mechanical signals from cell swelling and initiate volume regulatory are poorly understood. The purpose of this study was to investigate how the expression of two putative osmolyte channels (TRPV4 and BKCa) in chondrocytes is modulated in different osmotic conditions and to examine a potential role for MAPKs in this process. Isolated equine articular chondrocytes were subjected to anisosmotic conditions and the expression of the TRPV4 andBK_Ca channels and also ERK1/2 and p38 MAPKs protein phosphorylation were investigated using western blotting. Results indicated that TRPV4 contributes to the early stages of hypo-osmotic stress, while BK_Ca is involved in responses to elevated of intracellular Ca²⁺ and mediating regulatory volume decrease (RVD). ERK1/2 is phosphorylated by hypo-osmotic stress (P<0.001), and p38 MAPK is phosphorylated by hyper-osmotic stress (P<0.001). In addition this study demonstrated the importance of endogenous ERK1/2 phosphorylation in the expression of TRPV4 channel where blocking ERK1/2 by specific inhibitor (PD89059) significantly decreased endogenous level of the TRPV4 channel in cells exposed to hypo-osmotic stress and below endogenous levels in iso-osmotic conditions (P<0.001).