Curcumin, a component of the spice turmeric (Curcuma longa), has been reported to alleviate the symptoms of muscular dystrophy in mdx mice (Pan et al., 2008) and decrease the expression of inflammatory mediators involved in muscle injury (Epstein et al., 2012). Therefore, curcumin could provide an new avenue for the treatment of muscle disorders (Pan et al., 2008; Alamdari et al., 2009; Epstein et al., 2012). However, curcumin has also been reported to impair skeletal muscle Ca2+ handling (Bilmen et al., 2001; Logan-Smith et al., 2001), which could result in curcumin-induced muscle weakness. The aim of this study was to investigate the acute effects of curcumin exposure on skeletal muscle contractile function using intact and skinned fibre preparations from isolated extensor digitorum longus (EDL) muscles of the mouse. ARC(s) mice (male, 6 week old, n=12) were anaesthetized with sodium pentobarbitone (40 mg/kg, I.P.) and intact EDL muscles were surgically removed and attached to a force transducer system. Muscles were maintained in an organ bath containing Kreb’s mammalian Ringer solution, bubbled with carbogen (95% O2 and 5% CO2) at 25°C. The contractile properties (twitch force parameters, maximum tetanic force, force-stimulation frequency relationship and rate of muscle fatigue) were compared after a 60 minute exposure to curcumin or vehicle (0.01% DMSO). To determine the effect of curcumin on the Ca2+ sensitivity of the myofilaments, chemically skinned EDL fibres were exposed to highly buffered Ca2+ solutions of different known Ca2+ concentrations, in the presence of curcumin or DMSO. All values are expressed as means ± SEM. Curcumin (15µM) significantly decreased maximum specific force in whole EDL muscles (control: 21.84±0.64 N/cm2; curcumin: 19.07±0.57 N/cm2, p<0.05), and shifted the force-frequency relationship to the left, with significantly greater relative forces at stimulation frequencies of 10-80Hz in the curcumin group (p<0.05). Curcumin also significantly increased the time to peak force of the twitch response (control: 17±1 ms; curcumin: 20±1 ms, p<0.05), but had no significant effect on other twitch force parameters. In addition, the rate of muscle fatigue was significantly slower in the curcumin exposed group, compared to controls (p<0.05, n=6). In skinned fibre experiments, curcumin (15µM) produced a small increase in the sensitivity of the myofilaments to Ca2+ (pCa50: -6.26±0.05; control pCa50: -6.13±0.09, p<0.05), and a marked decrease maximal force production to 52.8±10.6% of controls (p<0.05). These findings show that, at a bath concentration of 15µM, curcumin significantly decreases maximal force production in skeletal muscle, most likely via a direct effect on the force generating ability of the myofilaments. These findings have important implications for the use of curcumin as a treatment for diseases resulting in skeletal muscle weakness.