期刊
TOXICON
卷 182, 期 -, 页码 13-20出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.toxicon.2020.04.096
关键词
Scorpion toxin; Neurite outgrowth; Sodium channel
资金
- National Key New Drug Creation and Manufacturing Program, Ministry of Science and Technology [2018YFF0215200]
- National Natural Science Foundation of China [81473539, 81903826, 81972960]
- China Postdoctoral Science Foundation [2018M630645, 2018M642371]
- East South University, China [2242019K3DZ01]
- China Pharmaceutical University
Scorpion venom is a rich source of bioactive compounds that affect neuronal excitability by modulating the activities of various channels/receptors. In the current study, guided by a Ca2+ mobilization assay, we purified a new neuroactive peptide designated as BmK NSP (Buthus martensii Karsch neurite-stimulating peptide, MW: 7064.30 Da). The primary structure of BmK NSP was determined by Edman degradation. BmK NSP concentration-dependently elevated intracellular Ca2+ concentration ([Ca2+](i)) with an EC50 value of 4.18 mu M in primary cultured spinal cord neurons (SCNs). Depletion of extracellular Ca2+ abolished BmK NSP-triggered Ca2+ response. Moreover, we demonstrated that BmK NSP-induced Ca2+ response was partially suppressed by the inhibitors of L-type Ca2+ channels, Na+-Ca2+ exchangers and NMDA receptors and was abolished by voltage-gated sodium channel (VGSC) blocker, tetrodotoxin. Whole-cell patch clamp recording demonstrated that BmK NSP delayed VGSC inactivation (EC50 = 1.10 mu M) in SCNs. BmK NSP enhanced neurite outgrowth in a non-monotonic manner that peaked at similar to 30 nM in SCNs. BmK NSP-promoted neurite outgrowth was suppressed by the inhibitors of L-type Ca2+ channels, NMDA receptors, and VGSCs. Considered together, these data demonstrate that BmK NSP is a new alpha-scorpion toxin that enhances neurite outgrowth through main routes of Ca2+ influx. Modulation of VGSC activity by alpha-scorpion toxin might represent a novel strategy to regulate the neurogenesis in SCNs.
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