In this paper, we investigated the action of huwentoxin-I (HWTX-I) purified from the venom of the Chinese bird spider Ornithoctonus huwena on Ca2+, Na+ channels of adult rat dorsal root ganglion (DRG) neurons. The results showed that huwentoxin-I could reduce the peak currents of N-type Ca2+ channels (IC50 approximate to 100 nM) and TTX-S Na+ channels (IC50 approximate to 55 nM), whereas no effect was detected on TTX-R Na+ channels. The comparative studies indicated that the selectivity of HWTX-I on Ca2+ channels was higher that of MVIIA and approximately the same as that of GVIA. HWTX-I is the first discovered toxin with the cross channel activities from the spider O. huwena venom similar to mu O-conotoxins MrVIA and MrVIB. (c) 2007 Published by Elsevier Inc.