Inhibitory Effects of Honokiol on the Voltage-Gated Potassium Channels in Freshly Isolated Mouse Dorsal Root Ganglion Neurons

摘要

Voltage-gated potassium (K-V) currents, subdivided into rapidly inactivating A-type currents (I-A) and slowly inactivating delayed rectifier currents (I-K), play a fundamental role in modulating pain by controlling neuronal excitability. The effects of Honokiol (Hon), a natural biphenolic compound derived from Magnolia officinalis, on K-V currents were investigated in freshly isolated mouse dorsal root ganglion neurons using the whole-cell patch clamp technique. Results showed that Hon inhibited I-A and I-K in concentration-dependent manner. The IC50 values for block of I-A and I-K were 30.5 and 25.7 mu M, respectively. Hon (30 mu M) shifted the steady-state activation curves of I-A and I-K to positive potentials by 17.6 and 16.7 mV, whereas inactivation and recovery from the inactivated state of I-A were unaffected. These results suggest that Hon preferentially interacts with the active states of the I-A and I-K channels, and has no effect on the resting state and inactivated state of the I-A channel. Blockade on K+ channels by Hon may contribute to its antinociceptive effect, especially anti-inflammatory pain.