Effects of a polyacetylene from Panax ginseng on Na⁺ currents in rat dorsal root ganglion neurons

The root of ginseng (Panax ginseng) has been used as a traditional medicine in the far east countries since ancient times. Ginseng extracts produce analgesia among other various biologically beneficial effects. A polyacetylenic compound, (9R,10S)-epoxyheptadecan-4,6-diyn-3-one (EHD), has been isolated from ginseng extract, whose biological activity is largely unknown. Voltage-gated Na⁺ channels in primary sensory neurons play important roles in pain perception. We investigated the effects of EHD on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na⁺ currents in acutely dissociated rat dorsal root ganglion neurons. EHD inhibited both Na⁺ currents in a concentration-dependent manner with an equal potency (K_d values were both 14.3 μM). The activation voltage was not affected by EHD in either type of Na⁺ current. However, EHD accelerated the inactivation of both Na⁺ currents and produced a hyperpolarizing shift of the steady-state inactivation curve. In addition EHD suppressed the maximal Na⁺ current at negative holding potentials at which the channels are relieved from inactivation. Thus EHD appears to bind both resting and inactivated channels. The recovery from inactivation of both Na⁺ currents was also slowed by EHD. EHD inhibition of TTX-S Na⁺ current but not TTX-R Na⁺ current was frequency-dependent. This is the first report that a polyacetylene from ginseng inhibits Na⁺ currents in primary sensory neurons. EHD by inhibiting Na⁺ currents may contribute to the ginseng analgesia.