Local anaesthetics (LAs) are routinely injected into joints at high concentrations during joint surgery [1], although consistent findings show local anaesthetics are chondrotoxic [2,3]. Studies have shown that LAs modulate both potassium and sodium channels, but the mechanism of cell chondrotoxicity is not known. In previous studies, we have shown that both transient receptor potential (TRP) channels and epithelial sodium channels (ENaC) exert a profound effect over chondrocyte cellular volume control and therefore interaction with these channels could potentially also be toxic [4, 5]. In this study we investigate whether any of a range of LAs modulate either ENaC-like channel activity and/or that of a TRP-like non-specific cation (NSC) conductance. Articular chondrocytes were isolated from canine stifle joints using standard procedures [4] from dogs euthanatized for unrelated veterinary reasons under local Ethical Approval. Standard physiological HEPES buffered saline solutions (150mM NaCl/5mM KCl) were included in both patch pipette and bath solutions. Membrane potentials were corrected for junction potential calculated using JPCalc (University of New South Wales, Auz). Ion channel activity was recorded in cell-attached mode. LAs were added to the patch pipette solution at typical clinical concentrations as follows: 20mM prilocaine, 35mM mepivacaine, 70mM mepivacaine and 15mM bupivacaine. Statistical tests were performed with Minitab (PA, USA). We first characterised an NSC single channel conductance, g of 43±13pS (n=14), sensitive to gadolinium III (75±9% reduction of open probability with 100µM), with a reversal potential (Vrev) of 1±9mV (n=14) and an ENaC-like ion channel (8.2±2.6pS, n=5) with Vrev 75±9mV (n=5) near to the predicted ENa of 85mV. The NSC channel was seen in 14/20 patches under control conditions, and the ENaC-like channel seen in 5/20 patches. Following exposure of the cells to each of the LAs there were no significant (ANOVA), changes in Vrev or g of the NSC channel (20mM prilocaine:-2±9mV, 45±9pS, n=4; 35mM mepivacaine 5±10mV, 65±16pS, n=9; 70mM mepivacaine 5±2mV, 31±5pS, n=6; 15mM bupivacaine 5±5mV, 67±25pS, n=6). However, this conductance was seen significantly more frequently in the presence of mepivacaine and bupivacaine (p<0.05, p<0.01 respectively; one sample sign test), but not prilocaine. No ENaC-like channel activity was detected in the presence of any of the local anaesthetic treatments used. This data shows that at the concentrations used routinely in clinics, local anaesthetics have profound effects on a chondrocyte ion channel activity. Future studies will be directed at establishing whether these acute ion channel effects do mediate decreases in chondrocyte survival.