Mechanism of action of a polypeptide neurotoxin from the coral Goniopora on sodium channels in mouse neuroblastoma cells.
Goniopora toxin (GPT), a polypeptide toxin of 9700 Da isolated from coral, markedly slows inactivation of sodium currents recorded under voltage clamp in mouse neuroblastoma cells. The voltage dependence of sodium channel activation is shifted to more negative membrane potentials by 9.8 +/- 2.1 mV, and the voltage dependence of channel inactivation is shifted to more positive membrane potential by 6.0 +/- 2.5 mV. These actions of GPT are voltage dependent with an e-fold increase in K0.5 for toxin action for each 48.3-mV depolarization between -80 and +40 mV. GPT requires Na+ or another alkali metal cation in the extracellular medium for its effect on sodium channels. The relative effectiveness of the different cations tested is Na+ greater than K+ greater than Rb+ greater than Li+ greater than Cs+ much greater than choline+. Like other polypeptide neurotoxins that slow inactivation of sodium channels, GPT enhances persistent activation of sodium channels by veratridine. However, GPT does not block the binding of 125I-labeled Leiurus scorpion toxin to neurotoxin receptor site 3 on sodium channels at concentrations which effectively slow channel inactivation. Therefore, our results define a new site on the sodium channel at which specific effects on inactivation can occur.
Gonoi
T
T
Ashida
K
K
Feller
D
D
Schmidt
J
J
Fujiwara
M
M
Catterall
W A
WA
D000200:Action Potentials; D000818:Animals; D002460:Cell Line; D002586:Cesium / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000187:drug effects*; D008433:Mathematics; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D010455:Peptides; D002586:Cesium; D013779:Tetrodotoxin; C020348:goniopora toxin; D012964:Sodium; D002794:Choline