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

Abstract

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, (9 R,10 S)-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.