Inhibition of neuronal tetrodotoxin-sensitive Na+ channels by two spider toxins:: hainantoxin-III and hainantoxin-IV

被引:59
作者
Xiao, XC [1 ]
Liang, SP [1 ]
机构
[1] Hunan Normal Univ, Coll Life Sci, Changsha 410081, Hunan, Peoples R China
关键词
spider toxin; dorsal ganglion neuron; Na+ current; patch-clamp; whole-cell;
D O I
10.1016/S0014-2999(03)02190-3
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Hainantoxin-III and hainantoxin-IV, isolated from the venom of the Chinese bird spider Seleconosmia hainana, are neurotoxic peptides composed of 33-35 residues with three disulfide bonds. Using whole-cell patch-clamp technique, we investigated their action on ionic channels of adult rat dorsal root ganglion neurons. It was found that the two toxins did not affect Ca2+ channels (both high voltage activated and low voltage activated types) nor tetrodotoxin-resistant voltage-gated Na+ channels (VGSCs). However, hainantoxin-III and hainantoxin-IV strongly depressed the amplitude of tetrodotoxin-sensitive Na+ currents with IC50 values of 1.1 and 44.6 nM, respectively. Both hainantoxin-III (1 nM) and hainantoxin-IV (50 nM) caused a hyperpolarizing shift of about 10 mV in the voltage midpoint of steady-state Na+ channel inactivation, but they showed difference in the reprime kinetics of VGSCs: hainantoxin-III significantly decreased the recovery rate from inactivation at a prepulse potential of -80 mV while hainantoxin-IV did not do. It is interesting to note that similar to huwentoxin-IV, the two hainantoxins did not affect the activation and inactivation kinetics of Na+ currents and at a concentration of 1 muM they completely inhibited the slowing inactivation currents induced by BMK-I (toxin I from the scorpion Buthus martensi Karsch), a scorpion alpha-like toxin. The results indicate that hainantoxin-III and hainantoxin-IV are novel spider toxins and affect the mammal neural Na+ channels through a mechanism quite different from other spider toxins targeting the neural receptor site 3, such as delta-aractoxins and mu-agatoxins. (C) 2003 Elsevier B.V. All rights reserved.
引用
收藏
页码:1 / 7
页数:7
相关论文
共 21 条
[1]  
ARAUJO DAM, 1993, N-S ARCH PHARMACOL, V347, P205
[2]   ALPHA-SCORPION TOXINS BINDING ON RAT-BRAIN AND INSECT SODIUM-CHANNELS REVEAL DIVERGENT ALLOSTERIC MODULATIONS BY BREVETOXIN AND VERATRIDINE [J].
CESTELE, S ;
KHALIFA, RB ;
PELHATE, M ;
ROCHAT, H ;
GORDON, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (25) :15153-15161
[3]   Structure and pharmacology of spider venom neurotoxins [J].
Escoubas, P ;
Diochot, S ;
Corzo, G .
BIOCHIMIE, 2000, 82 (9-10) :893-907
[4]  
Grolleau F, 2001, J EXP BIOL, V204, P711
[5]  
Ji YH, 1996, TOXICON, V34, P987, DOI 10.1016/0041-0101(96)00065-7
[6]  
LIANG SP, 1999, LIFE SCI RES, V3, P299
[7]  
Liu ZH, 2002, ACTA BIOCH BIOPH SIN, V34, P516
[8]   INHIBITION OF N-TYPE AND L-TYPE CA2+ CHANNELS BY THE SPIDER VENOM TOXIN OMEGA-AGA-IIIA [J].
MINTZ, IM ;
VENEMA, VJ ;
ADAMS, ME ;
BEAN, BP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (15) :6628-6631
[9]   Characterisation of the effects of robustoxin, the lethal neurotoxin from the Sydney funnel-web spider Atrax robustus, on sodium channel activation and inactivation [J].
Nicholson, GM ;
Walsh, R ;
Little, MJ ;
Tyler, MI .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1998, 436 (01) :117-126
[10]  
OGATA N, 1993, J PHYSIOL-LONDON, V466, P9