A new toxin from the sea anemone Condylactis gigantea with effect on sodium channel inactivation.
A new peptide toxin exhibiting a molecular weight of 5043Da (av.) and comprising 47 amino acid residues was isolated from the sea anemone Condylactis gigantea. Purification of the peptide was achieved by a multistep chromatographic procedure monitoring its strong paralytic activity on crustacea (LD(50) approx. 1microg/kg). Complete sequence analysis of the toxic peptide revealed the isolation of a new member of type I sea anemone sodium channel toxins containing the typical pattern of the six cysteine residues. From 11kg of wet starting material, approximately 1g of the peptide toxin was isolated. The physiological action of the new toxin from C. gigantea CgNa was investigated on sodium currents of rat dorsal root ganglion neurons in culture using whole-cell patch clamp technique (n=60). Under current clamp condition (CgNa) increased action potential duration. This effect is due to slowing down of the TTX-S sodium current inactivation, without modifying the activation process. CgNa prolonged the cardiac action potential duration and enhanced contractile force albeit at 100-fold higher concentrations than the Anemonia sulcata toxin ATXII. The action on sodium channel inactivation and on cardiac excitation-contraction coupling resemble previous results with compounds obtained from this and other sea anemones [Shapiro, B.I., 1968. Purification of a toxin from tentacles of the anemone C. gigantea. Toxicon 5, 253-259; Pelhate, M., Zlotkin, E., 1982. Actions of insect toxin and other toxins derived from the venom of scorpion Androtonus australis on isolated giant axons of the cockroach Periplaneta americana. J. Exp. Biol. 97, 67-77; Salgado, V., Kem, W., 1992. Actions of three structurally distinct sea anemone toxins on crustacean and insect sodium channels. Toxicon 30, 1365-1381; Bruhn, T., Schaller, C., Schulze, C., Sanchez-Rodriquez, J., Dannmeier, C., Ravens, U., Heubach, J.F., Eckhardt, K., Schmidtmayer, J., Schmidt, H., Aneiros, A., Wachter, E., Béress, L., 2001. Isolation and characterization of 5 neurotoxic and cardiotoxic polypeptides from the sea anemone Anthopleura elegantissima. Toxicon, 39, 693-702]. Comprehensive analysis of the purified active fractions suggests that CgNa may represent the main peptide toxin of this sea anemone species.
Ständker
Ludger
L
IPF PharmaCeuticals GmbH, Feodor-Lynen Strasse 31, 30625 Hannover, Germany. L.standker@gmx.de
Béress
Lászlo
L
Garateix
Anoland
A
Christ
Torsten
T
Ravens
Ursula
U
Salceda
Emilio
E
Soto
Enrique
E
John
Harald
H
Forssmann
Wolf-Georg
WG
Aneiros
Abel
A
D000595:Amino Acid Sequence; D000818:Animals; D003386:Brachyura / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003064:Cnidarian Venoms / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D008387:Marine Toxins / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects / Q000503:physiopathology; D010243:Paralysis / Q000139:chemically induced / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D012615:Sea Anemones / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D015222:Sodium Channels / Q000187:drug effects
D003064:Cnidarian Venoms; D008387:Marine Toxins; D026941:Sodium Channel Blockers; D015222:Sodium Channels