Characterization of a Novel Gastropod Toxin (6-Bromo-2-mercaptotryptamine) That Inhibits Shaker K Channel Activity

• Published in: The Journal of biological chemistry 2003-09, Vol.278 (37), p.34934-34942
• Main Authors: Kelley, Wayne P., Wolters, Andrew M., Sack, Jon T., Jockusch, Rebecca A., Jurchen, John C., Williams, Evan R., Sweedler, Jonathan V., Gilly, William F.
• Format: Article
• Language: English
• Subjects: 6-bromo-2-mercaptotryptamine; Animals; Calliostoma canaliculatum; Chromatography, High Pressure Liquid; Disulfides - chemistry; Disulfides - isolation & purification; Disulfides - pharmacology; Female; hypobranchial gland; Magnetic Resonance Spectroscopy; Marine; Oocytes - drug effects; Oocytes - physiology; Potassium Channel Blockers - chemistry; Potassium Channel Blockers - isolation & purification; Potassium Channel Blockers - pharmacology; potassium channels; Potassium Channels - physiology; Recombinant Proteins - drug effects; Shaker Superfamily of Potassium Channels; Snails; Spectrometry, Mass, Electrospray Ionization; Tryptamines - chemistry; Tryptamines - isolation & purification; Tryptamines - pharmacology; Xenopus laevis
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M301271200

A novel potassium channel antagonist has been purified from the defensive mucus secreted by Calliostoma canaliculatum, a marine snail found in the temperate coastal waters of the western Pacific. The toxin is expelled from the hypobranchial gland as part of a defensive response and is contained within a viscous matrix that minimizes dilution and degradation. The active compound was isolated by multistage microbore HPLC separations followed by bioactivity assays. Nuclear magnetic resonance, combined with electrospray ionization Fourier-transform ion cyclotron resonance and electrospray ionization ion trap mass spectrometry indicate that the active component is a heretofore unknown indole-derivative, a disulfide-linked dimer of 6-bromo-2-mercaptotryptamine (BrMT). Exudates from the hypobranchial glands of various marine mollusks have been sources for dye compounds such as 6–6 dibromoindigo, the ancient dye Tyrian purple. BrMT represents the first correlation of a hypobranchial gland exudate with a molecular response. Voltage clamp experiments with a number of K channel subtypes indicate that BrMT inhibits certain voltage-gated K channels of the Kv1 subfamily.