The interaction of polypeptide neurotoxins with tetrodotoxin-resistant Na+ channels in mammalian cardiac cells. Correlation with inotropic and arrhythmic effects.
This paper describes the interaction of several polypeptide neurotoxins isolated from sea anemone toxins and scorpion venom with the tetrodotoxin-resistant Na+ channel of rat cardiac cells. The 22Na+ flux and tension development were measured to examine in parallel the cardiotonic and cardiotoxic effects of these polypeptides. Inotropic effects and arrhythmias were seen in the concentration range in which an action of the toxins on the Na+ channel was observed. The maximal inotropic effect was systematically observed at toxin concentrations below the concentration value observed for half-maximal stimulation of 22Na+ flux through the Na+ channel. Arrhythmias began at concentrations near the value for half-maximal stimulation of 22Na+ flux by the toxins. Toxins extracted from the sea anemones Anemonia sulcata and Anthopleura xanthogrammica were more active than scorpion toxins and sea anemone Radianthus paumotensis toxins. The most interesting among all the toxins tested for potential use in cardiotherapy was toxin II from Anthopleura xanthogrammica.
Renaud
J F
JF
Fosset
M
M
Schweitz
H
H
Lazdunski
M
M
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D002478:Cells, Cultured; D003064:Cnidarian Venoms / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D012604:Scorpion Venoms / Q000494:pharmacology; D012615:Sea Anemones; D013779:Tetrodotoxin / Q000494:pharmacology*
D003064:Cnidarian Venoms; D007473:Ion Channels; D009498:Neurotoxins; D012604:Scorpion Venoms; D013779:Tetrodotoxin