1.Scorpion toxin BmK I directly activates Nav1.8 in primary sensory neurons to induce neuronal hyperexcitability in rats.
Pin YE ; Yunlu JIAO ; Zhenwei LI ; Liming HUA ; Jin FU ; Feng JIANG ; Tong LIU ; Yonghua JI
Protein & Cell 2015;6(6):443-452
Voltage-gated sodium channels (VGSCs) in primary sensory neurons play a key role in transmitting pain signals to the central nervous system. BmK I, a site-3 sodium channel-specific toxin from scorpion Buthus martensi Karsch, induces pain behaviors in rats. However, the subtypes of VGSCs targeted by BmK I were not entirely clear. We therefore investigated the effects of BmK I on the current amplitude, gating and kinetic properties of Nav1.8, which is associated with neuronal hyperexcitability in DRG neurons. It was found that BmK I dose-dependently increased Nav1.8 current in small-sized (<25 μm) acutely dissociated DRG neurons, which correlated with its inhibition on both fast and slow inactivation. Moreover, voltage-dependent activation and steady-state inactivation curves of Nav1.8 were shifted in a hyperpolarized direction. Thus, BmK I reduced the threshold of neuronal excitability and increased action potential firing in DRG neurons. In conclusion, our data clearly demonstrated that BmK I modulated Nav1.8 remarkably, suggesting BmK I as a valuable probe for studying Nav1.8. And Nav1.8 is an important target related to BmK I-evoked pain.
Aniline Compounds
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pharmacology
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Animals
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Cell Size
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Cells, Cultured
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Electrophysiological Phenomena
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drug effects
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Furans
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pharmacology
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Ganglia, Spinal
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cytology
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Kinetics
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Male
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NAV1.8 Voltage-Gated Sodium Channel
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metabolism
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Rats
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Rats, Sprague-Dawley
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Scorpion Venoms
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antagonists & inhibitors
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pharmacology
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Scorpions
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Sensory Receptor Cells
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drug effects
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metabolism
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physiology
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Sodium Channel Blockers
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pharmacology
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Voltage-Gated Sodium Channel Agonists
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pharmacology