Effects of BmKNJX11, a bioactive polypeptide purified from Buthus martensi Karsch, on sodium channels in rat dorsal root ganglion neurons.
A long-chain polypeptide BmKNJX11 was purified from the venom of Asian scorpion Buthus martensi Karsch (BmK) by a combination of gel filtration, ion-exchange chromatography, and reverse-phase high-performance liquid chromatography. The molecular mass was found to be 7036.85 Da by electrospray ionization mass spectrometry. The first 15 N-terminal amino acid sequence of BmKNJX11 was determined to be GRDAY IADSE NCTYT by Edman degradation. With whole cell recording, BmKNJX11 inhibited tetrodotoxin-sensitive voltage-gated sodium channels (TTX-S VGSC) in freshly isolated rat dorsal root ganglion (DRG) neurons in a concentration- and voltage-dependent manner. At a concentration of 40 mug/ml BmKNJX11 lowered the activation threshold and produced negative shifting of TTX-S sodium current (I(Na)) activation curve. In addition, BmKNJX11 induced shifting of the steady-state inactivation curve to the left, delayed the recovery of TTX-S I(Na) 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-S VGSC expressed in DRG neurons play a critical role in nociceptive transmission, the interaction of BmKNJX11 with TTX-S VGSC might lead to a change in excitability of nociceptive afferent fibers, which may be involved in the observed peripheral pain expression.
Wang
Xi-Jie
XJ
Laboratory of Neurotoxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People's Republic China.
An
Shan-Shan
SS
Cheng
Hong
H
Xu
San-Hua
SH
Cheng
Jie
J
Lu
Wei
W
Gao
Rong
R
Xiao
Hang
H
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects*; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D008970:Molecular Weight; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000302:isolation & purification / Q000494:pharmacology*; D012605:Scorpions / Q000737:chemistry*; D015222:Sodium Channels / Q000187:drug effects*; D014118:Toxins, Biological / Q000302:isolation & purification / Q000494:pharmacology*
C535147:BmKNJX11; D010455:Peptides; D012604:Scorpion Venoms; D015222:Sodium Channels; D014118:Toxins, Biological