The alpha-like scorpion toxin BmK I enhances membrane excitability via persistent sodium current by preventing slow inactivation and deactivation of rNav1.2a expressed in Xenopus Oocytes.
BmK I is classified as alpha-like scorpion toxin that specifically binds the voltage-gated sodium channels via receptor site-3. Previous results showed BmK I induced epileptiform responses in rats via intra-hippocampal injection, but the mechanism has yet to be clarified. In this study, using two-electrode voltage/current clamp technique, we determined the effects of BmK I on rNav1.2a expressed in Xenopus oocytes. The results showed that BmK I prevented the development of slow inactivation of rNav1.2a from the open-state and enhanced the persistent sodium current (I(NaP)) at suprathreshold potentials in concentration-dependence, whereas it hardly affected the fast inactivation. BmK I was also able to augment the subthreshold I(NaP) at high concentrations (>100nM) with disruption of the open-state deactivation. The increased I(NaP) accelerated the firing frequency in the oocytes that fired repetitively after electrode punctures, as well as raised the baseline potential and induced bursting of spikes in the quiescent oocytes. These results demonstrated that BmK I could target rNav1.2a and induce the I(NaP) by preventing the development of slow inactivation and deactivation from the open-state, leading to the enhancement of membrane excitability, which may be involved in the BmK I-induced epilepsy.
Zhu
Mang-Mang
MM
Graduate School of Chinese Academy of Sciences, Shanghai Institute of Physiology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China. mmzhu@sibs.ac.cn
Tan
Miao
M
Cheng
Hui-Wen
HW
Ji
Yong-Hua
YH
D000818:Animals; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009865:Oocytes / Q000378:metabolism; D051381:Rats; D012604:Scorpion Venoms / Q000633:toxicity*; D015222:Sodium Channels / Q000187:drug effects* / Q000235:genetics; D014982:Xenopus laevis / Q000235:genetics
D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568253:Scn2A protein, rat; D012604:Scorpion Venoms; D015222:Sodium Channels; C105338:makatoxin I