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Scorpion toxin BmK I directly activates Nav1.8 in primary sensory neurons to induce neuronal hyperexcitability in rats
| Content Provider | Paperity |
|---|---|
| Author | Li, Zhenwei Hua, Liming Jiao, Yunlu Fu, Jin Liu, Tong Ji, Yonghua Ye, Pin Jiang, Feng |
| Abstract | 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. |
| Starting Page | 443 |
| Ending Page | 452 |
| File Format | HTM / HTML |
| ISSN | 1674800X |
| DOI | 10.1007/s13238-015-0154-4 |
| Issue Number | 6 |
| Journal | Protein & Cell |
| Volume Number | 6 |
| e-ISSN | 16748018 |
| Language | English |
| Publisher | SpringerOpen |
| Publisher Date | 2015-06-01 |
| Access Restriction | Open |
| Subject Keyword | Primary sensory neurons Bmk i Voltage-gated sodium channel Nav1.8 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Drug Discovery Biochemistry Biotechnology |