The ciliary neurotrophic factor (CNTF), known to exert long-term myotrophic effects, is not yet evidenced to induce a rapid biological response in skeletal muscles. The present in vitro study brings up the possibility that CNTF could affect the sodium channel activity implied in the triggering of muscle fibre contraction. Therefore, we investigated the effects of an external CNTF application on macroscopic sodium current (INa) in rat native fast-twitch skeletal muscle (flexor digitorum brevis, FDB) by using a cell-attached patch-clamp technique. The INa peak amplitude measured at a depolarising pulse from -100 to -10mV is rapidly reduced in a time- and dose-dependent manner by CNTF (0.01-20 ng ml-1). The maximal decrease is 25% after 10 minutes incubation in 2ng ml-1 CNTF. Neither activation and inactivation kinetics, nor activation curves constructed from current-voltage relationships are altered in the presence of CNTF. In the opposite, the relative INa inhibition induced by CNTF is accompanied by a hyperpolarizing shift in the midpoint of inactivation curves: -6 and -10mV for the steady-state fast and slow inactivation respectively. Furthermore, CNTF induces a 5mV hyperpolarization of the resting membrane potential of the fibres. CNTF effects are similar to those of OAG, a PKC activator when no effect is observed in the presence of chelerythrine, a PKC inhibitor. These results suggest that, in skeletal muscle CNTF can rapidly decrease sodium currents by altering inactivation gating, probably through an intracellular PKC-dependent mechanism that could lead to decreased membrane excitability. The present study would contribute to a better understanding of the physiological role of endogenous CNTF.