Effects of free fatty acids on sodium currents in rat dorsal root ganglion neurons

Free fatty acids (FFAs), especially polyunsaturated fatty acids (PUFAs), are potent modulators of muscle-type sodium channels. It is not known if they also modulate sodium channels of sensory neurons. In this study, we investigated the effects of FFAs on the fast tetrodotoxin-sensitive (fTTX-S) and the slow tetrodotoxin-resistant (sTTX-R) sodium currents in rat dorsal root ganglion neurons. At a holding potential of -80 mV, PUFAs potently inhibited fTTX-S current, but monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs) to a lesser extent. All FFAs initially increased sTTX-R current, and then decreased it slightly. PUFAs and MUFAs produced a hyperpolarizing shift of the steady-state inactivation voltage for both types of sodium currents. The shift generally increased with the number of unsaturated bonds. FFAs did not change the maximum amplitude of fTTX-S current, but increased that of sTTX-R current. Most FFAs shifted the activation voltage for fTTX-S current in the hyperpolarizing direction, which was not dependent on the degree of unsaturation. MUFAs and SFAs shifted the activation voltage for sTTX-R current in the hyperpolarizing direction, but PUFAs were without effect. The modulation of sodium currents by FFAs, especially PUFAs, may have considerable impact on the excitability of sensory neurons.