Characterization of a novel gastropod toxin (6-bromo-2-mercaptotryptamine) that inhibits shaker K channel activity.
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.
Kelley
Wayne P
WP
Department of Chemistry and the Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61820, USA.
Wolters
Andrew M
AM
Sack
Jon T
JT
Jockusch
Rebecca A
RA
Jurchen
John C
JC
Williams
Evan R
ER
Sweedler
Jonathan V
JV
Gilly
William F
WF
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004220:Disulfides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D011994:Recombinant Proteins / Q000187:drug effects; D051637:Shaker Superfamily of Potassium Channels; D012908:Snails; D021241:Spectrometry, Mass, Electrospray Ionization; D014363:Tryptamines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014982:Xenopus laevis
D004220:Disulfides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011994:Recombinant Proteins; D051637:Shaker Superfamily of Potassium Channels; D014363:Tryptamines; C478480:bis(6-bromo-2-mercaptotryptamin-2-yl)disulfide