东亚钳蝎毒素多肽BmKNJX11对大鼠背根神经节TTX-R型钠通道的作用

BmKNJX11is a 7036.85 Da polypeptide purified from the venom of Asian scorpion Buthus martensi Karsch (BmK). With whole cell recording, BmKNJX11 inhibited tetrodotoxin- resistant voltage-gated sodium channels (TTX-R VGSC) in freshly isolated rat dorsal root ganglion (DRG) neurons in a concentration- and voltage-dependent manner. At a concentration of 40 μg/ml BmKNJX11 increased the activation threshold and produced positive shifting of TTX-R sodium current (INa) activation curve. In addition, BmKNJX11 induced shifting of the steady-state inactivation curve to left, delayed the recovery of TTX-R INa from inactivation, and also reduced the fraction of available sodium channels. These results suggested that BmKNJX11 might exert effects on VGSC by binding to a specific site. Considering that TTX-R VGSC expressed in DRG neurons play a critical role in nociceptive transmission, the interaction of BmKNJX11 with TTX-R VGSC might lead to a change in excitability of nociceptive afferent fibers which may be involved in the observed peripheral pain expression.