The site of action of Ptychodiscus brevis toxin within the parasympathetic axonal sodium channel h gate in airway smooth muscle.
The red tide toxin produced by Ptychodiscus brevis ( PBTX ) may cause cough, sneezing, and asthma. Previous in vitro studies with isolated canine tracheal smooth muscle demonstrated that PBTX stimulates sodium channels of parasympathetic nerve endings and thus causes a contractile response. The present study investigated the mechanism of the PBTX effect on canine tracheal smooth muscle. Repeated exposure of the muscle strip to PBTX (final concentration 46 micrograms/ml) followed by washout of the toxin resulted in reestablishment of baseline tension but a failure of contraction on further addition of PBTX . However, veratridine and scorpion toxin (SCT), which are voltage-sensitive sodium channel activators, still induced contraction. Furthermore, the contraction caused by veratridine was enhanced by a high dose of PBTX , whereas contraction caused by SCT was not. Responses to veratridine and SCT as well as PBTX (previously reported) were blocked by tetrodotoxin (a sodium channel blocker), while acetylcholine responsiveness remained intact. These results indicate that PBTX receptors in parasympathetic nerves influence Na+ flux at the h gate, that these receptors differ from the veratridine and SCT receptors, and that the conformational change in the receptors induced by PBTX affects the tissue response to veratridine.
D000818:Animals; D001369:Axons / Q000187:drug effects; D004141:Dinoflagellida / Q000276:immunology*; D004285:Dogs; D007473:Ion Channels / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000294:innervation*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D012605:Scorpions; D013779:Tetrodotoxin / Q000494:pharmacology; D014118:Toxins, Biological / Q000494:pharmacology*; D014132:Trachea / Q000294:innervation; D014701:Veratridine / Q000494:pharmacology
D007473:Ion Channels; D014118:Toxins, Biological; D013779:Tetrodotoxin; D014701:Veratridine