The modulation effects of BmK I, an alpha-like scorpion neurotoxin, on voltage-gated Na(+) currents in rat dorsal root ganglion neurons.

The present study investigated the effects of BmK I, a Na(+) channel receptor site 3 modulator purified from the Buthus martensi Karsch (BmK) venom, on the voltage-gated sodium currents in dorsal root ganglion (DRG) neurons. Whole-cell patch-clamping was used to record the tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) components of voltage-gated Na(+) currents in small DRG neurons. It was found that the inhibitory effect of BmK I on open-state inactivation of TTX-S Na(+) currents was stronger than that of TTX-R Na(+) currents. In addition, BmK I exhibited a selective enhancing effect on voltage-dependent activation of TTX-S currents, and an opposite effect on time-dependent activation of TTX-S and TTX-R Na(+) currents. The results suggested that the inhibitory effect of BmK I on open-state inactivation might contribute to the increase of peak TTX-S and TTX-R currents, and the enhancing effect of BmK I on time-dependent activation might also contribute to the increase of peak TTX-S currents. It was further suggested that a combined effect of BmK I including inhibiting the inactivation of TTX-S and TTX-R channels, accelerating activation and decreasing the activation threshold of TTX-S channels, might produce a hyperexcitability of small DRG neurons, and thus contribute to the BmK I-induced hyperalgesia.