Effects of ApC, a sea anemone toxin, on sodium currents of mammalian neurons.
We have characterized the actions of ApC, a sea anemone polypeptide toxin isolated from Anthopleura elegantissima, on neuronal sodium currents (I(Na)) using current and voltage-clamp techniques. Neurons of the dorsal root ganglia of Wistar rats (P5-9) in primary culture were used for this study. These cells express tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) I(Na). In current-clamp experiments, application of ApC increased the average duration of the action potential. Under voltage-clamp conditions, the main effect of ApC was a concentration-dependent increase in the TTX-S I(Na) inactivation time course. No significant effects were observed on the activation time course or on the current peak-amplitude. ApC also produced a hyperpolarizing shift in the voltage at which 50% of the channels are inactivated and caused a significant decrease in the voltage dependence of Na+ channel inactivation. No effects were observed on TTX-R I(Na). Our results suggest that ApC slows the conformational changes required for fast inactivation of the mammalian Na+ channels in a form similar to other site-3 toxins, although with a greater potency than ATX-II, a highly homologous anemone toxin.
Salceda
Emilio
E
Instituto de Fisiología, Universidad Autónoma de Puebla, Apartado Postal 406, Puebla, Pue, CP 72001, Mexico. esalceda@siu.buap.mx
Garateix
Anoland
A
Aneiros
Abel
A
Salazar
Héctor
H
López
Omar
O
Soto
Enrique
E
D000818:Animals; D002478:Cells, Cultured; D003064:Cnidarian Venoms / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000145:classification / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012615:Sea Anemones / Q000737:chemistry*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
C515208:ApC toxin; D003064:Cnidarian Venoms; D009498:Neurotoxins; D010455:Peptides; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin