Skip to main content
SpringerLink
Log in

Activation of sodium channels by α-scorpion toxin, BmK NT1, produced neurotoxicity in cerebellar granule cells: an association with intracellular Ca2+ overloading

  • Organ Toxicity and Mechanisms
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Voltage-gated sodium channels (VGSCs) are responsible for the action potential generation in excitable cells including neurons and involved in many physiological and pathological processes. Scorpion toxins are invaluable tools to explore the structure and function of ion channels. BmK NT1, a scorpion toxin from Buthus martensii Karsch, stimulates sodium influx in cerebellar granule cells (CGCs). In this study, we characterized the mode of action of BmK NT1 on the VGSCs and explored the cellular response in CGC cultures. BmK NT1 delayed the fast inactivation of VGSCs, increased the Na+ currents, and shifted the steady-state activation and inactivation to more hyperpolarized membrane potential, which was similar to the mode of action of α-scorpion toxins. BmK NT1 stimulated neuron death (EC50 = 0.68 µM) and produced massive intracellular Ca2+ overloading (EC50 = 0.98 µM). TTX abrogated these responses, suggesting that both responses were subsequent to the activation of VGSCs. The Ca2+ response of BmK NT1 was primary through extracellular Ca2+ influx since reducing the extracellular Ca2+ concentration suppressed the Ca2+ response. Further pharmacological evaluation demonstrated that BmK NT1-induced Ca2+ influx and neurotoxicity were partially blocked either by MK-801, an NMDA receptor blocker, or by KB-R7943, an inhibitor of Na+/Ca2+ exchangers. Nifedipine, an L-type Ca2+ channel inhibitor, slightly suppressed both Ca2+ response and neurotoxicity. A combination of these three inhibitors abrogated both responses. Considered together, these data ambiguously demonstrated that activation of VGSCs by an α-scorpion toxin was sufficient to produce neurotoxicity which was associated with intracellular Ca2+ overloading through both NMDA receptor- and Na+/Ca2+ exchanger-mediated Ca2+ influx.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

AUC:

Area under the curve

CGCs:

Cerebellar granule cells

CI:

Confidence intervals

DIV:

Days in vitro

DMSO:

Dimethyl sulfoxide

FDA:

Fluorescein diacetate

LDH:

Lactate dehydrogenase

NMDA:

N-methyl-d-aspartate

PbTxs:

Brevetoxins

PI:

Propidium iodide

TTX:

Tetrodotoxin

VGSCs:

Voltage-gated sodium channels

References

  • Altafaj X, France J, Almassy J et al (2007) Maurocalcine interacts with the cardiac ryanodine receptor without inducing channel modification. Biochem J 406(2):309–315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barbosa TM, Morais JE, Forte P, Neiva H, Garrido ND, Marinho DA (2015) A comparison of experimental and analytical procedures to measure passive drag in human swimming. PLoS One 10(7):e0130868

    Article  PubMed  PubMed Central  Google Scholar 

  • Bergeron ZL, Bingham JP (2012) Scorpion toxins specific for potassium (K+) channels: a historical overview of peptide bioengineering. Toxins 4(11):1082–1119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berman FW, Murray TF (1996) Characterization of glutamate toxicity in cultured rat cerebellar granule neurons at reduced temperature. J Biochem Toxicol 11(3):111–119

    Article  CAS  PubMed  Google Scholar 

  • Berman FW, Murray TF (1999) Brevetoxins cause acute excitotoxicity in primary cultures of rat cerebellar granule neurons. J Pharmacol Exp Ther 290(1):439–444

    CAS  PubMed  Google Scholar 

  • Berman FW, Murray TF (2000) Brevetoxin-induced autocrine excitotoxicity is associated with manifold routes of Ca2+ influx. J Neurochem 74(4):1443–1451

    Article  CAS  PubMed  Google Scholar 

  • Bicalho AF, Guatimosim C, Prado MA, Gomez MV, Romano-Silva MA (2002) Investigation of the modulation of glutamate release by sodium channels using neurotoxins. Neuroscience 113(1):115–123

    Article  CAS  PubMed  Google Scholar 

  • Braidy N, Grant R, Adams S, Brew BJ, Guillemin GJ (2009) Mechanism for quinolinic acid cytotoxicity in human astrocytes and neurons. Neurotox Res 16(1):77–86

    Article  CAS  PubMed  Google Scholar 

  • Caliskan F, Quintero-Hernandez V, Restano-Cassulini R, Coronas-Valderrama FI, Corzo G, Possani LD (2013) Molecular cloning and biochemical characterization of the first Na(+)-channel alpha-type toxin peptide (Acra4) from Androctonus crassicauda scorpion venom. Biochimie 95(6):1216–1222

    Article  CAS  PubMed  Google Scholar 

  • Cao Z, George J, Gerwick WH, Baden DG, Rainier JD, Murray TF (2008) Influence of lipid-soluble gating modifier toxins on sodium influx in neocortical neurons. J Pharmacol Exp Ther 326(2):604–613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cao Z, Gerwick WH, Murray TF (2010) Antillatoxin is a sodium channel activator that displays unique efficacy in heterologously expressed rNav1.2, rNav1.4 and rNav1.5 alpha subunits. BMC Neurosci 11:154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cao Z, Shafer TJ, Murray TF (2011) Mechanisms of pyrethroid insecticide-induced stimulation of calcium influx in neocortical neurons. J Pharmacol Exp Ther 336(1):197–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cao Z, Hulsizer S, Tassone F et al (2012) Clustered burst firing in FMR1 premutation hippocampal neurons: amelioration with allopregnanolone. Hum Mol Genet 21(13):2923–2935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cao Z, Cui Y, Nguyen HM, Jenkins DP, Wulff H, Pessah IN (2014a) Nanomolar bifenthrin alters synchronous Ca2+ oscillations and cortical neuron development independent of sodium channel activity. Mol Pharmacol 85(4):630–639

    Article  PubMed  PubMed Central  Google Scholar 

  • Cao Z, Di Z, Wu Y, Li W (2014b) Overview of scorpion species from China and their toxins. Toxins 6(3):796–815

    Article  PubMed  PubMed Central  Google Scholar 

  • Cao Z, Li X, Zou X, Greenwood M, Gerwick WH, Murray TF (2015a) Involvement of JNK and caspase activation in hoiamide A-induced neurotoxicity in neocortical neurons. Mar Drugs 13(2):903–919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cao Z, Zou X, Cui Y et al (2015b) Rapid throughput analysis demonstrates that chemicals with distinct seizurogenic mechanisms differentially alter Ca2+ dynamics in networks formed by hippocampal neurons in culture. Mol Pharmacol 87(4):595–605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Catterall WA, Cestele S, Yarov-Yarovoy V, Yu FH, Konoki K, Scheuer T (2007) Voltage-gated ion channels and gating modifier toxins. Toxicon 49(2):124–141

    Article  CAS  PubMed  Google Scholar 

  • Cestele S, Qu Y, Rogers JC, Rochat H, Scheuer T, Catterall WA (1998) Voltage sensor-trapping: enhanced activation of sodium channels by beta-scorpion toxin bound to the S3–S4 loop in domain II. Neuron 21(4):919–931

    Article  CAS  PubMed  Google Scholar 

  • Chahine M, Chatelier A, Babich O, Krupp JJ (2008) Voltage-gated sodium channels in neurological disorders. CNS Neurol Disord Drug Targets 7(2):144–158

    Article  CAS  PubMed  Google Scholar 

  • Chai ZF, Zhu MM, Bai ZT et al (2006) Chinese-scorpion (Buthus martensii Karsch) toxin BmK alphaIV, a novel modulator of sodium channels: from genomic organization to functional analysis. Biochem J 399(3):445–453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen Y, Stevens B, Chang J, Milbrandt J, Barres BA, Hell JW (2008) NS21: re-defined and modified supplement B27 for neuronal cultures. J Neurosci Methods 171(2):239–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cohen L, Karbat I, Gilles N et al (2005) Common features in the functional surface of scorpion beta-toxins and elements that confer specificity for insect and mammalian voltage-gated sodium channels. J Biol Chem 280(6):5045–5053

    Article  CAS  PubMed  Google Scholar 

  • Cohen L, Troub Y, Turkov M et al (2007) Mammalian skeletal muscle voltage-gated sodium channels are affected by scorpion depressant “insect-selective” toxins when preconditioned. Mol Pharmacol 72(5):1220–1227

    Article  CAS  PubMed  Google Scholar 

  • Ekberg J, Craik DJ, Adams DJ (2008) Conotoxin modulation of voltage-gated sodium channels. Int J Biochem Cell Biol 40(11):2363–2368

    Article  CAS  PubMed  Google Scholar 

  • 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 Vitro 22(6):1582–1587

    Article  CAS  PubMed  Google Scholar 

  • Gadagkar SR, Call GB (2015) Computational tools for fitting the Hill equation to dose–response curves. J Pharmacol Toxicol Methods 71:68–76

    Article  CAS  PubMed  Google Scholar 

  • Gaddis ML, Gaddis GM (1990) Introduction to biostatistics: part 6, correlation and regression. Ann Emerg Med 19(12):1462–1468

    Article  CAS  PubMed  Google Scholar 

  • Garcia ML, Hanner M, Knaus HG, Slaughter R, Kaczorowski GJ (1999) Scorpion toxins as tools for studying potassium channels. Methods Enzymol 294:624–639

    Article  CAS  PubMed  Google Scholar 

  • George J, Dravid SM, Prakash A et al (2009) Sodium channel activation augments NMDA receptor function and promotes neurite outgrowth in immature cerebrocortical neurons. J Neurosci 29(10):3288–3301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • George J, Baden DG, Gerwick WH, Murray TF (2012) Bidirectional influence of sodium channel activation on NMDA receptor-dependent cerebrocortical neuron structural plasticity. Proc Natl Acad Sci USA 109(48):19840–19845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goudet C, Huys I, Clynen E et al (2001) Electrophysiological characterization of BmK M1, an alpha-like toxin from Buthus martensii Karsch venom. FEBS Lett 495(1–2):61–65

    Article  CAS  PubMed  Google Scholar 

  • Goudet C, Chi CW, Tytgat J (2002) An overview of toxins and genes from the venom of the Asian scorpion Buthus martensii Karsch. Toxicon 40(9):1239–1258

    Article  CAS  PubMed  Google Scholar 

  • He X, Liu X, Zeng Z et al (2000) Crystal structure determination of a neutral neurotoxin BmK M4 from Buthus martensii Karsch at 0.20 nm. Sci China Ser C Life Sci 43(1):39–46

    Article  CAS  Google Scholar 

  • 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 J 431(2):289–298

    Article  CAS  PubMed  Google Scholar 

  • Hidalgo P, MacKinnon R (1995) Revealing the architecture of a K+ channel pore through mutant cycles with a peptide inhibitor. Science 268(5208):307–310

    Article  CAS  PubMed  Google Scholar 

  • Hothorn L (1994) Multiple comparisons in long-term toxicity studies. Environ Health Perspect 102(Suppl 1):33–38

    Article  PubMed  PubMed Central  Google Scholar 

  • Ji YH, Wang WX, Ye JG et al (2003) Martentoxin, a novel K+-channel-blocking peptide: purification, cDNA and genomic cloning, and electrophysiological and pharmacological characterization. J Neurochem 84(2):325–335

    Article  CAS  PubMed  Google Scholar 

  • Koh JY, Choi DW (1987) Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. J Neurosci Methods 20(1):83–90

    Article  CAS  PubMed  Google Scholar 

  • Lange A, Giller K, Hornig S et al (2006) Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR. Nature 440(7086):959–962

    Article  CAS  PubMed  Google Scholar 

  • Lee CW, Lee EH, Takeuchi K, Takahashi H, Shimada I (2004) Molecular basis of the high-affinity activation of type 1 ryanodine receptors by imperatoxin A. Biochem J 377(2):385–394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee CW, Bae C, Lee J et al (2012) Solution structure of kurtoxin: a gating modifier selective for Cav3 voltage-gated Ca2+ channels. Biochemistry 51(9):1862–1873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leipold E, Hansel A, Borges A, Heinemann SH (2006) Subtype specificity of scorpion beta-toxin Tz1 interaction with voltage-gated sodium channels is determined by the pore loop of domain 3. Mol Pharmacol 70(1):340–347

    CAS  PubMed  Google Scholar 

  • Li WI, Berman FW, Okino T et al (2001) Antillatoxin is a marine cyanobacterial toxin that potently activates voltage-gated sodium channels. Proc Natl Acad Sci USA 98(13):7599–7604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu T, Pang XY, Bai ZT, Chai ZF, Jiang F, Ji YH (2007) Intrathecal injection of glutamate receptor antagonists/agonist selectively attenuated rat pain-related behaviors induced by the venom of scorpion Buthus martensii Karsch. Toxicon 50(8):1073–1084

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Li C, Chen J et al (2014) AGAP, a new recombinant neurotoxic polypeptide, targets the voltage-gated calcium channels in rat small diameter DRG neurons. Biochem Biophys Res Commun 452(1):60–65

    Article  CAS  PubMed  Google Scholar 

  • MacKinnon R, Miller C (1989) Mutant potassium channels with altered binding of charybdotoxin, a pore-blocking peptide inhibitor. Science 245(4924):1382–1385

    Article  CAS  PubMed  Google Scholar 

  • MacKinnon R, Cohen SL, Kuo A, Lee A, Chait BT (1998) Structural conservation in prokaryotic and eukaryotic potassium channels. Science 280(5360):106–109

    Article  CAS  PubMed  Google Scholar 

  • Maertens C, Cuypers E, Amininasab M, Jalali A, Vatanpour H, Tytgat J (2006) Potent modulation of the voltage-gated sodium channel Nav1.7 by OD1, a toxin from the scorpion Odonthobuthus doriae. Mol Pharmacol 70(1):405–414

    CAS  PubMed  Google Scholar 

  • Mello DF, de Oliveira ES, Vieira RC et al (2012) Cellular and transcriptional responses of Crassostrea gigas hemocytes exposed in vitro to brevetoxin (PbTx-2). Mar Drugs 10(3):583–597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noelker C, Morel L, Osterloh A et al (2014) Heat shock protein 60: an endogenous inducer of dopaminergic cell death in Parkinson disease. J Neuroinflamm 11:86

    Article  Google Scholar 

  • Patino GA, Isom LL (2010) Electrophysiology and beyond: multiple roles of Na+ channel beta subunits in development and disease. Neurosci Lett 486(2):53–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pereira A, Cao Z, Murray TF, Gerwick WH (2009) Hoiamide a, a sodium channel activator of unusual architecture from a consortium of two papua new Guinea cyanobacteria. Chem Biol 16(8):893–906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pineda SS, Undheim EA, Rupasinghe DB, Ikonomopoulou MP, King GF (2014) Spider venomics: implications for drug discovery. Future Med Chem 6(15):1699–1714

    Article  CAS  PubMed  Google Scholar 

  • Quintero-Hernandez V, Jimenez-Vargas JM, Gurrola GB, Valdivia HH, Possani LD (2013) Scorpion venom components that affect ion-channels function. Toxicon 76:328–342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramirez-Bello V, Sevcik C, Peigneur S, Tytgat J, D’Suze G (2014) Macrophage alteration induced by inflammatory toxins isolated from Tityus discrepans scorpion venom. The role of Na(+)/Ca(2+) exchangers. Toxicon 82:61–75

    Article  CAS  PubMed  Google Scholar 

  • Ramonet D, Rodriguez MJ, Fredriksson K, Bernal F, Mahy N (2004) In vivo neuroprotective adaptation of the glutamate/glutamine cycle to neuronal death. Hippocampus 14(5):586–594

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez de la Vega RC, Possani LD (2005) Overview of scorpion toxins specific for Na+ channels and related peptides: biodiversity, structure-function relationships and evolution. Toxicon 46(8):831–844

    Article  CAS  PubMed  Google Scholar 

  • Rowe AH, Xiao Y, Rowe MP, Cummins TR, Zakon HH (2013) Voltage-gated sodium channel in grasshopper mice defends against bark scorpion toxin. Science 342(6157):441–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruigt GS, Neyt HC, Van der Zalm JM, Van den Bercken J (1987) Increase of sodium current after pyrethroid insecticides in mouse neuroblastoma cells. Brain Res 437(2):309–322

    Article  CAS  PubMed  Google Scholar 

  • Sattler R, Xiong Z, Lu WY, MacDonald JF, Tymianski M (2000) Distinct roles of synaptic and extrasynaptic NMDA receptors in excitotoxicity. J Neurosci 20(1):22–33

    CAS  PubMed  Google Scholar 

  • Schwade JG, Makuch RW, Strong JM, Glatstein E (1982) Dose–response curves for predicting misonidazole-induced peripheral neuropathy. Cancer Treat Rep 66(9):1743–1750

    CAS  PubMed  Google Scholar 

  • Shashanka M, Raj B, Smaragdis P (2008) Probabilistic latent variable models as nonnegative factorizations. Comput Intell Neurosci. doi:10.1155/2008/947438

    PubMed  PubMed Central  Google Scholar 

  • Silva RF, Falcao AS, Fernandes A, Gordo AC, Brito MA, Brites D (2006) Dissociated primary nerve cell cultures as models for assessment of neurotoxicity. Toxicol Lett 163(1):1–9

    Article  CAS  PubMed  Google Scholar 

  • Southan AP, Robertson B (2000) Electrophysiological characterization of voltage-gated K(+) currents in cerebellar basket and purkinje cells: Kv1 and Kv3 channel subfamilies are present in basket cell nerve terminals. J Neurosci 20(1):114–122

    CAS  PubMed  Google Scholar 

  • Stevens M, Peigneur S, Tytgat J (2011) Neurotoxins and their binding areas on voltage-gated sodium channels. Front Pharmacol 2:71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ullrich N, Bordey A, Gillespie GY, Sontheimer H (1998) Expression of voltage-activated chloride currents in acute slices of human gliomas. Neuroscience 83(4):1161–1173

    Article  CAS  PubMed  Google Scholar 

  • Valdivia HH, Martin BM, Ramirez AN, Fletcher PL, Possani LD (1994) Isolation and pharmacological characterization of four novel Na+ channel-blocking toxins from the scorpion Centruroides noxius Hoffmann. J Biochem 116(6):1383–1391

    CAS  PubMed  Google Scholar 

  • Vandendriessche T, Olamendi-Portugal T, Zamudio FZ, Possani LD, Tytgat J (2010) Isolation and characterization of two novel scorpion toxins: The alpha-toxin-like CeII8, specific for Na(v)1.7 channels and the classical anti-mammalian CeII9, specific for Na(v)1.4 channels. Toxicon 56(4):613–623

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Yarov-Yarovoy V, Kahn R et al (2011) Mapping the receptor site for alpha-scorpion toxins on a Na+ channel voltage sensor. Proc Natl Acad Sci USA 108(37):15426–15431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weimer M, Jiang X, Ponta O, Stanzel S, Freyberger A, Kopp-Schneider A (2012) The impact of data transformations on concentration-response modeling. Toxicol Lett 213(2):292–298

    Article  CAS  PubMed  Google Scholar 

  • Xu X, Duan Z, Di Z et al (2014) Proteomic analysis of the venom from the scorpion Mesobuthus martensii. J Proteomics 106:162–180

    Article  CAS  PubMed  Google Scholar 

  • Yang S, Liu Z, Xiao Y et al (2012) Chemical punch packed in venoms makes centipedes excellent predators. Mol Cell Proteomics MCP 11(9):640–650

    Article  CAS  PubMed  Google Scholar 

  • Yu XM, Salter MW (1998) Gain control of NMDA-receptor currents by intracellular sodium. Nature 396(6710):469–474

    Article  CAS  PubMed  Google Scholar 

  • Zeng XC, Luo F, Li WX (2006) Molecular dissection of venom from Chinese scorpion Mesobuthus martensii: identification and characterization of four novel disulfide-bridged venom peptides. Peptides 27(7):1745–1754

    Article  CAS  PubMed  Google Scholar 

  • Zhang JZ, Yarov-Yarovoy V, Scheuer T et al (2011) Structure-function map of the receptor site for beta-scorpion toxins in domain II of voltage-gated sodium channels. J Biol Chem 286(38):33641–33651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang JZ, Yarov-Yarovoy V, Scheuer T et al (2012) Mapping the interaction site for a beta-scorpion toxin in the pore module of domain III of voltage-gated Na(+) channels. J Biol Chem 287(36):30719–30728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu SY, Li WX, Zeng XC, Liu H, Jiang DH, Mao X (2000) Nine novel precursors of Buthus martensii scorpion alpha-toxin homologues. Toxicon 38(12):1653–1661

    Article  CAS  PubMed  Google Scholar 

  • Zou X, He Y, Qiao J, Zhang C, Cao Z (2016) The natural scorpion peptide, BmK NT1 activates voltage-gated sodium channels and produces neurotoxicity in primary cultured cerebellar granule cells. Toxicon 109:33–41

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by National Natural Science Foundation of China (Nos. 81473539, 81570696, and 31270985); National High Technology Research and Development Program of China (863 Program, 2015AA020314); Jiangsu Provincial Natural Science Foundation (BK20141357); The Program For Jiangsu Province Innovative Research Team and The Program For Jiangsu Province Innovative Research Individual.

Author information

Author notes

    Authors and Affiliations

    1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, Jiangsu, People’s Republic of China

      Yuwei He, Xiaohan Zou, Xichun Li, Juan Chen, Liang Jin, Fan Zhang, Boyang Yu & Zhengyu Cao

    2. Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, China Pharmaceutical University, Nanjing, 211198, Jiangsu, People’s Republic of China

      Yuwei He, Xiaohan Zou, Xichun Li, Juan Chen, Fan Zhang, Boyang Yu & Zhengyu Cao

    3. School of Biological Pharmaceutics, China Pharmaceutical University, Nanjing, 211198, Jiangsu, People’s Republic of China

      Liang Jin

    Authors
    1. Yuwei He
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Xiaohan Zou
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Xichun Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Juan Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Liang Jin
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Fan Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Boyang Yu
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Zhengyu Cao
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Fan Zhang or Zhengyu Cao.

    Ethics declarations

    Conflict of interest

    The authors declare no conflicts of interest.

    Additional information

    Yuwei He and Xiaohan Zou have contributed equally in this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    He, Y., Zou, X., Li, X. et al. Activation of sodium channels by α-scorpion toxin, BmK NT1, produced neurotoxicity in cerebellar granule cells: an association with intracellular Ca2+ overloading. Arch Toxicol 91, 935–948 (2017). https://doi.org/10.1007/s00204-016-1755-2

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00204-016-1755-2

    Keywords

    Search

    Navigation