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. (C) 2004 Elsevier B.V. All rights reserved.