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Article

BmK NSPK, a Potent Potassium Channel Inhibitor from Scorpion Buthus martensii Karsch, Promotes Neurite Outgrowth via NGF/TrkA Signaling Pathway

Department of TCM Pharmacology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 3 December 2020 / Revised: 30 December 2020 / Accepted: 31 December 2020 / Published: 5 January 2021
(This article belongs to the Special Issue Animal Venoms and Their Components: Molecular Mechanisms of Action)
Scorpion toxins represent a variety of tools to explore molecular mechanisms and cellular signaling pathways of many biological functions. These toxins are also promising lead compounds for developing treatments for many neurological diseases. In the current study, we purified a new scorpion toxin designated as BmK NSPK (Buthus martensii Karsch neurite-stimulating peptide targeting Kv channels) from the BmK venom. The primary structure was determined using Edman degradation. BmK NSPK directly inhibited outward K+ current without affecting sodium channel activities, depolarized membrane, and increased spontaneous calcium oscillation in spinal cord neurons (SCNs) at low nanomolar concentrations. BmK NSPK produced a nonmonotonic increase on the neurite extension that peaked at ~10 nM. Mechanistic studies demonstrated that BmK NSPK increased the release of nerve growth factor (NGF). The tyrosine kinases A (TrkA) receptor inhibitor, GW 441756, eliminated the BmK NSPK-induced neurite outgrowth. BmK NSPK also increased phosphorylation levels of protein kinase B (Akt) that is the downstream regulator of TrkA receptors. These data demonstrate that BmK NSPK is a new voltage-gated potassium (Kv) channel inhibitor that augments neurite extension via NGF/TrkA signaling pathway. Kv channels may represent molecular targets to modulate SCN development and regeneration and to develop the treatments for spinal cord injury. View Full-Text
Keywords: neurite outgrowth; scorpion toxin; potassium channel; nerve growth factor neurite outgrowth; scorpion toxin; potassium channel; nerve growth factor
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MDPI and ACS Style

Zhao, F.; Zou, X.; Li, S.; He, J.; Xi, C.; Tang, Q.; Wang, Y.; Cao, Z. BmK NSPK, a Potent Potassium Channel Inhibitor from Scorpion Buthus martensii Karsch, Promotes Neurite Outgrowth via NGF/TrkA Signaling Pathway. Toxins 2021, 13, 33. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13010033

AMA Style

Zhao F, Zou X, Li S, He J, Xi C, Tang Q, Wang Y, Cao Z. BmK NSPK, a Potent Potassium Channel Inhibitor from Scorpion Buthus martensii Karsch, Promotes Neurite Outgrowth via NGF/TrkA Signaling Pathway. Toxins. 2021; 13(1):33. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13010033

Chicago/Turabian Style

Zhao, Fang, Xiaohan Zou, Shaoheng Li, Jing He, Chuchu Xi, Qinglian Tang, Yujing Wang, and Zhengyu Cao. 2021. "BmK NSPK, a Potent Potassium Channel Inhibitor from Scorpion Buthus martensii Karsch, Promotes Neurite Outgrowth via NGF/TrkA Signaling Pathway" Toxins 13, no. 1: 33. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13010033

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