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

Abstract

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.

Functional Characterization of a New Degradation Peptide BmTX4-P1 from Traditional Chinese Scorpion Medicinal Material

“…The traditional Chinese scorpion medicinal materials are obtained from wild Buthus martensii Karsch scorpions. To date, there have been many studies on neurotoxins from the venom of Buthus martensii Karsch scorpions, from which a large number of neurotoxins that act on ion channels have been found [ 2 , 3 , 4 , 5 , 6 , 7 ]; some neurotoxins were considered to have the potential to treat diseases [ 8 , 9 , 10 , 11 , 12 ]. However, there had been no report on the peptide components of scorpion medicinal materials for a long time.…”

Animal Venoms and Their Components: Molecular Mechanisms of Action

“…The results obtained suggest that toxin loop III may participate in the effective interaction of some long-chain neurotoxins with a GABA A receptor. From the venom of the scorpion Buthus martensii, the new toxin BmK NSPK was isolated [7]. The toxin inhibits outward K+ current without affecting sodium channel, depolarized membrane, and increased spontaneous calcium oscillation in spinal cord neurons.…”