Magnolol inhibits sodium currents in freshly isolated mouse dorsal root ganglion neurons.

Abstract

The voltage-gated sodium channel (VGSC) currents in dorsal root ganglion (DRG) neurons contain mainly TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na+ currents. Magnolol (Mag), a hydroxylated biphenyl compound isolated from the bark of Magnolia officinalis, has been well documented to exhibit analgesic effects, but its mechanism is not yet fully understood. The aim of the present study was to investigate whether the antinociceptive effects of Mag is through inhibition of Na+ currents. Na+ currents in freshly isolated mouse DRG neurons were recorded with the whole cell patch clamp technique. Results showed that Mag inhibited TTX-S and TTX-R Na+ currents in a concentration-dependent manner. The IC50 values for block of TTX-S and TTX-R Na+ currents were 9.4 and 7.0μmol/L, respectively. Therefore, TTX-R Na+ current was more susceptible to Mag than TTX-S Na+ current. For TTX-S Na+ channel, 10μmol/L Mag shifted the steady state inactivation curve toward more negative by 9.8mV, without affecting the activation curve. For TTX-R Na+ channel, 7μmol/L Mag shifted the steady state activation and inactivation curves toward more positive and negative potentials by 6.5 and 11.7mV, respectively. In addition, Mag significantly postponed recovery of TTX-S and TTX-R Na+ currents from inactivation, and produced frequency dependent blocks of both subtypes of Na+ currents. These results suggest that the inhibitory effects of Mag on Na+ channels may contribute to its analgesic effect.