# Molecular Basis of the Inhibition of Voltage-Gated Potassium Channel Kv1.1 by Chinese Tarantula Peptide Huwentoxin-XI

## TL;DR

This study explores how a Chinese tarantula toxin, HWTX-XI, selectively blocks a specific potassium channel, Kv1.1, and its potential use in pain research.

## Contribution

The study identifies the molecular mechanism by which HWTX-XI inhibits Kv1.1 and demonstrates its analgesic potential.

## Key findings

- HWTX-XI selectively blocks Kv1.1 channels without affecting other ion channels.
- Mutation of Tyr379 in the filter region reduces HWTX-XI's affinity by 90-fold.
- HWTX-XI reduces pain sensitivity and increases neuronal firing in mice.

## Abstract

Huwentoxin-XI (HWTX-XI) is a 55-amino acid peptide belonging to the family of spider Kuntiz-type toxins (KTTs), isolated from the venom of the Chinese tarantula Cyriopagopus schmidti. Under whole-cell voltage-clamp conditions, HWTX-XI was found to block Kv1.1 potassium channels but had no effect on other potassium channel subunits (Kv1.4, Kv2.1, Kv3.1 and Kv4.2), sodium channels or calcium channels. In the present study, it was found that the substitution of Tyr379 by the valine in the filter region significantly decreased the affinity of toxin HWTX-XI by about 90-fold, indicating that the Kv1.1 filter region is a critical determinant of HWTX-XI potassium channel activity. After intrathecal or intraplantar injections, HWTX-XI decreased the mechanical nociceptive threshold (hyperalgesia) for a long-lasting period. HWTX-XI also significantly increased the firing frequency in mouse DRG neurons. The novel function of HWTX-XI makes it a new tool for studying the relationship between spider toxins and Kv1.1 channels and suggests that Kv1.1 channels might be a novel potential target for preventing and/or treating neuropathic pain.