Parkinson's disease-like forelimb akinesia induced by BmK I, a sodium channel modulator.
Parkinson's disease (PD) is a neurodegenerative disorder and characterized by motor disabilities which are mostly linked with high levels of synchronous oscillations in the basal ganglia neurons. Voltage-gated sodium channels (VGSCs) play a vital role in the abnormal electrical activity of neurons in the globus pallidus (GP) and the subthalamic nucleus (STN) in PD. BmK I, a α-like toxin purified from the Chinese scorpion Buthus martensi Karsch, has been identified a site-3-specific modulator of VGSCs. The present study shows that forelimb akinesia can be induced by the injection of BmK I into the globus pallidus (GP) in rats. In addition, BmK I cannot produce neuronal damage in vivo and in vitro at 24h after treatment, indicating that the forelimb akinesia does not result from neuronal damage. Electrophysiological studies further revealed that the inactivated Na(+) currents were showed to be more vulnerably modulated by BmK I than the activated Na(+) currents in human neuron-like SHSY5Y cells. Furthermore, the modulation of BmK I on inactivation was preferentially attributed to fast inactivation rather than slow inactivation. Therefore, the PD-like forelimb akinesia may result from the modulation of sodium channels in neuron by BmK I. These findings not only suggest that BmK I may be an effective and novel molecule for the study of pathogenesis in PD but also support the idea that VGSCs play a crucial role in the motor disabilities in PD.
Laboratory of Neuropharmacology and Neurotoxicology, School of Life Science, Shanghai University, Shanghai, China. Electronic address: zhyred@shu.edu.cn.
Hongyan
H
Zhu
Laboratory of Neuropharmacology and Neurotoxicology, School of Life Science, Shanghai University, Shanghai, China. Electronic address: yhji@shu.edu.cn.
Ziyi
Z
Wang
Laboratory of Neuropharmacology and Neurotoxicology, School of Life Science, Shanghai University, Shanghai, China.
Jiahui
J
Jin
Laboratory of Neuropharmacology and Neurotoxicology, School of Life Science, Shanghai University, Shanghai, China.
Xiao
X
Pei
Laboratory of Neuropharmacology and Neurotoxicology, School of Life Science, Shanghai University, Shanghai, China.
Yuxiao
Y
Zhao
Laboratory of Neuropharmacology and Neurotoxicology, School of Life Science, Shanghai University, Shanghai, China.
Hao
H
Wu
Laboratory of Neuropharmacology and Neurotoxicology, School of Life Science, Shanghai University, Shanghai, China.
Weide
W
Lin
Laboratory of Neuropharmacology and Neurotoxicology, School of Life Science, Shanghai University, Shanghai, China.
Jie
J
Tao
Laboratory of Neuropharmacology and Neurotoxicology, School of Life Science, Shanghai University, Shanghai, China.
Yonghua
Y
Ji
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005552:Forelimb / Q000187:drug effects / Q000503:physiopathology*; D005917:Globus Pallidus / Q000187:drug effects / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D009447:Neuroblastoma / Q000473:pathology; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000494:pharmacology*; D015222:Sodium Channels / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D049990:Membrane Transport Modulators; D012604:Scorpion Venoms; D015222:Sodium Channels; C105338:makatoxin I; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
Forelimb akinesia; Parkinson disease; Voltage-gated Na(+) channels; α-Like scorpion toxin