Scorpion toxin BmK I directly activates Nav1.8 in primary sensory neurons to induce neuronal hyperexcitability in rats
Received date: 09 Feb 2015
Accepted date: 05 Mar 2015
Published date: 11 Jun 2015
Copyright
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 smallsized (<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.
Key words： voltage-gated sodium channel; Nav1.8; primary sensory neurons; BmK I
Pin Ye , Yunlu Jiao , Zhenwei Li , Liming Hua , Jin Fu , Feng Jiang , Tong Liu , Yonghua Ji . Scorpion toxin BmK I directly activates Nav1.8 in primary sensory neurons to induce neuronal hyperexcitability in rats[J]. Protein & Cell, 2015 , 6(6) : 443 -452 . DOI: 10.1007/s13238-015-0154-4
| 1 |
Agrawal N, Hamam BN, Magistretti J, Alonso A, Ragsdale DS (2001) Persistent sodium channel activity mediates subthreshold membrane potential oscillations and low-threshold spikes in rat entorhinal cortex layer V neurons. Neuroscience102: 53-64
|
| 2 |
Bai ZT, Liu T, Chai ZF, Pang XY, Ji YH (2006a) Rat pain-related responses induced by experimental scorpion BmK sting. Eur J Pharmacol552: 67-77
|
| 3 |
Bai ZT, Zhao R, Zhang XY, Chen J, Liu T, Ji YH (2006b) The epileptic seizures induced by BmK I, a modulator of sodium channels. Exp Neurol197: 167-176
|
| 4 |
Bai ZT, Liu T, Jiang F, Cheng M, Pang XY, Hua LM, Shi J, Zhou JJ, Shu XQ, Zhang JW
|
| 5 |
Bosmans F, Tytgat J (2007) Voltage-gated sodium channel modulation by scorpion alpha-toxins. Toxicon49: 142-158
|
| 6 |
Chen J, Tan ZY, Zhao R, Feng XH, Shi J, Ji YH (2005) The modulation effects of BmK I, an alpha-like scorpion neurotoxin, on voltage-gated Na(+) currents in rat dorsal root ganglion neurons. Neurosci Lett390: 66-71
|
| 7 |
Dib-Hajj SD, Cummins TR, Black JA, Waxman SG (2010) Sodium channels in normal and pathological pain. Annu Rev Neurosci33: 325-347
|
| 8 |
Ekberg J, Jayamanne A, Vaughan CW, Aslan S, Thomas L, Mould J, Drinkwater R, Baker MD, Abrahamsen B, Wood JN
|
| 9 |
Feng XH, Chen JX, Liu Y, Ji YH (2008) Electrophysiological characterization of BmK I, an alpha-like scorpion toxin, on rNav1.5 expressed in HEK293t cells. Toxicol In Vitro22: 1582-1587
|
| 10 |
Gold MS (1999) Tetrodotoxin-resistant Na+ currents and inflammatory hyperalgesia. Proc Natl Acad Sci USA96: 7645-7649
|
| 11 |
Gold MS, Reichling DB, Shuster MJ, Levine JD (1996) Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors. Proc Natl Acad Sci U S A93: 1108-1112
|
| 12 |
He H, Liu Z, Dong B, Zhou J, Zhu H, Ji Y (2010) Molecular determination of selectivity of the site 3 modulator (BmK I) to sodium channels in the CNS: a clue to the importance of Nav1.6 in BmK I-induced neuronal hyperexcitability. Biochem J431: 289-298
|
| 13 |
Ji YH, Mansuelle P, Terakawa S, Kopeyan C, Yanaihara N, Hsu K, Rochat H (1996) Two neurotoxins (BmK I and BmK II) from the venom of the scorpion Buthus martensi Karsch: purification, amino acid sequences and assessment of specific activity. Toxicon34: 987-1001
|
| 14 |
Joshi SK, Mikusa JP, Hernandez G, Baker S, Shieh CC, Neelands T, Zhang XF, Niforatos W, Kage K, Han P
|
| 15 |
Khasar SG, Gold MS, Levine JD (1998) A tetrodotoxin-resistant sodium current mediates inflammatory pain in the rat. Neurosci Lett256: 17-20
|
| 16 |
Knapp O, Nevin ST, Yasuda T, Lawrence N, Lewis RJ, Adams DJ (2012) Biophysical properties of Na(v) 1.8/Na(v) 1.2 chimeras and inhibition by microO-conotoxin MrVIB. Br J Pharmacol166: 2148-2160
|
| 17 |
McCleskey EW, Gold MS (1999) Ion channels of nociception. Annu Rev Physiol61: 835-856
|
| 18 |
Priest BT, Blumenthal KM, Smith JJ, Warren VA, Smith MM (2007) ProTx-I and ProTx-II: gating modifiers of voltage-gated sodium channels. Toxicon49: 194-201
|
| 19 |
Renganathan M, Cummins TR, Waxman SG (2001) Contribution of Na(v)1.8 sodium channels to action potential electrogenesis in DRG neurons. J Neurophysiol86: 629-640
|
| 20 |
Rogers JC, Qu Y, Tanada TN, Scheuer T, Catterall WA (1996) Molecular determinants of high affinity binding of alpha-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel alpha subunit. J Biol Chem271: 15950-15962
|
| 21 |
Tan ZY, Donnelly DF, LaMotte RH (2006) Effects of a chronic compression of the dorsal root ganglion on voltage-gated Na+ and K+ currents in cutaneous afferent neurons. J Neurophysiol95: 1115-1123
|
| 22 |
Tan ZY, Piekarz AD, Priest BT, Knopp KL, Krajewski JL, McDermott JS, Nisenbaum ES, Cummins TR (2014) Tetrodotoxin-resistant sodium channels in sensory neurons generate slow resurgent currents that are enhanced by inflammatory mediators. J Neurosci34: 7190-7197
|
| 23 |
Todd AJ (2010) Neuronal circuitry for pain processing in the dorsal horn. Nat Rev Neurosci11: 823-836
|
| 24 |
Yang Q, Wu Z, Hadden JK, Odem MA, Zuo Y, Crook RJ, Frost JA, Walters ET (2014) Persistent pain after spinal cord injury is maintained by primary afferent activity. J Neurosci34: 10765-10769
|
| 25 |
Zhu MM, Tan M, Cheng HW, Ji YH (2009) The alpha-like scorpion toxin BmK I enhances membrane excitability via persistent sodium current by preventing slow inactivation and deactivation of rNav1.2a expressed in Xenopus Oocytes. Toxicol In Vitro23: 561-568
|
| 26 |
Zimmermann M (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain16: 109-110
|
| 27 |
Zuo XP, Ji YH (2004) Molecular mechanism of scorpion neurotoxins acting on sodium channels: insight into their diverse selectivity. Mol Neurobiol30: 265-278
|
| 28 |
Zuo XP, He HQ, He M, Liu ZR, Xu Q, Ye JG, Ji YH (2006) Comparative pharmacology and cloning of two novel arachnid sodium channels: Exploring the adaptive insensitivity of scorpion to its toxins. FEBS Lett580:4508 -4514
|
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