Electrophysiological characterization of BmK I, an alpha-like scorpion toxin, on rNav1.5 expressed in HEK293t cells.
A recent study described the pharmacological properties of BmK I, an alpha-like toxin from the Chinese scorpion Buthus martensi Karsch, on the cardiac sodium channel (hH1) expressed in Xenopus oocytes. Considering that alpha-like toxins are unique in their inability to bind to rat synaptosomes despite a high toxicity by intravenous injection, the present study investigated the pharmacological properties of BmK I on rNav1.5 expressed in a mammalian HEK293t cell line. The results include: (1) BmK I slowed and partially inhibited the inactivation of rNav1.5, produced a substantial persistent current and increased peak current (the EC(50) for increasing peak current by BmK I was 99.4+/-20.1 nM); (2) BmK I delayed the recovery of the sodium channel from inactivation; (3) after exposure to 300nM BmK I, the steady-state activation curve of rNav1.5 was negatively shifted by about 19 mV; and (4) the association of BmK I and rNav1.5 was faster than their dissociation. The results show that BmK I displayed the pharmacological characteristics of an alpha-like toxin on rNav1.5 channels expressed in HEK293t cells, and suggested that the host expression system should be taken into consideration when characterizing the pharmacological properties of toxins.
Feng
Xing-Hua
XH
Graduate School of the Chinese Academy of Sciences, Shanghai Institute of Physiology, Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Chen
Jue-Xu
JX
Liu
Ying
Y
Ji
Yong-Hua
YH
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006801:Humans; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D012604:Scorpion Venoms / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D012605:Scorpions; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism
D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; C568322:Scn5a protein, rat; D012604:Scorpion Venoms; D015222:Sodium Channels; C105338:makatoxin I