New Sea Anemone Toxin RTX-VI Selectively Modulates Voltage-Gated Sodium Channels

Area of Science:

• Marine Biology
• Neuroscience
• Biochemistry

Background:

• Sea anemones produce potent neurotoxins that modulate ion channels.
• Voltage-gated sodium channels (Na_V) are crucial for nerve impulse propagation.
• Previous toxins like RTX-III have shown activity against Na_V channels.

Purpose of the Study:

• To isolate and characterize a new neurotoxin from the sea anemone *Heteractis crispa*.
• To determine the structure and functional properties of the novel toxin, RTX-VI.
• To investigate the selectivity of RTX-VI towards different subtypes of voltage-gated sodium channels.

Main Methods:

• Isolation of RTX-VI from *Heteractis crispa* ethanolic extract.
• Amino acid sequencing using Edman degradation and tandem mass spectrometry.
• Electrophysiological screening of RTX-VI on various Na_V channel subtypes.

Main Results:

• RTX-VI, a two-disulfide-linked peptide chain neurotoxin, was isolated.
• RTX-VI lacks Arg13, a residue critical for Na_V channel interaction in related toxins.
• Electrophysiology confirmed RTX-VI's selective modulation of central nervous system (Na_V1.2, Na_V1.6) and insect (BgNa_V1, VdNa_V1) sodium channels.

Conclusions:

• RTX-VI is a unique sea anemone toxin with a distinct structural feature (absence of Arg13).
• The novel toxin exhibits selective activity against specific neuronal and insect Na_V channel subtypes.
• RTX-VI represents a valuable new tool for studying Na_V channel function and diversity.