Novel Sodium Channel Inhibitor From Leeches

Area of Science:

• Biochemistry
• Neuroscience
• Pharmacology

Background:

• Leech saliva is known for pain reduction, but specific analgesic compounds remain unidentified.
• Clinical leech therapy demonstrates significant and prolonged pain relief, suggesting the presence of potent analgesics.

Purpose of the Study:

• To identify novel analgesic substances in the saliva of the leech *Haemadipsa sylvestris*.
• To investigate the mechanism of action of identified analgesic peptides on neuronal targets.

Main Methods:

• Identification and characterization of a novel peptide family (HSTXs) from leech salivary glands.
• Biochemical analysis of HSTX structure, including disulfide bridges and C-terminal amidation.
• Electrophysiological studies to assess the effect of HSTX-I on voltage-gated sodium channels (Na_V1.8 and Na_V1.9).

Main Results:

• A new family of 11 small peptides, HSTXs, with low similarity to known peptides was discovered.
• HSTX-I was found to significantly inhibit Na_V1.8 and Na_V1.9 channels.
• These specific sodium channels are crucial for neuronal action potential generation.

Conclusions:

• The identified HSTX peptides are responsible for the analgesic effects observed in leech saliva.
• HSTX-I functions as a sodium channel inhibitor, providing a mechanism for pain reduction.
• HSTXs represent valuable templates for the development of novel analgesics targeting specific sodium channels.