N-type Ca_v channel inhibition by spider venom peptide of Argiope bruennichi

Background: The spider venom is composed of various bioactive peptides and has well-known physiological characteristics, such as cytolytic and neurotoxic activities. However, there have been few studies on neurotoxic peptides derived from domestic indigenous spiders in Korea. Objective: The study aimed to characterize and identify the venom peptide through genomic analysis from the domestic indigenous spider, Argiope bruennichi. Toxin-like peptides were selected using homology analysis against well-known toxin peptides along with the secondary structural characterization analysis by cysteine pattern and disulfide bonds. Modulation of voltage-gated calcium (Ca_v) channel was measured by Ca²⁺ influx using fluorescence dye. Results: We found that a novel peptide Aranetoxin-Ab1a significantly reduced intracellular Ca²⁺ levels in human neuroblastoma cell line SH-SY5Y via the inactivation of N-type Ca_v channels. Decreased intracellular Ca²⁺ influx by the treatment of the peptide inactivated the extracellular-regulated protein kinase 1/2 and cAMP-response factor binding protein pathway. Conclusion: Our results provide beneficial information for the potential development of drugs utilizing novel peptide derived from spider venom, showing the inhibition of N-type Ca_v by the peptide.