title: Red tide toxin produces in vitro depolarization of human airway smooth muscle.
abstract: BACKGROUND
  Brevetoxin (PbTx), taken from the earlier species name Ptychodiscus brevis, is a red algae toxin. It has been associated with clinically observed bronchoconstriction in nonasthmatics. In asthmatics, similar exposures may produce severe transient effects, sometimes requiring emergency treatment, thus suggesting that asthmatics are more sensitive to this toxin. As such, we have investigated potential mechanisms in vitro.
  
  
  METHODS
  Membrane potentials of in vitro airway smooth muscle (ASM) preparations were measured with a microelectrode before, during, and after the exposure to PbTx (0.01-1.2 microg/mL) in strip preparations (SPs) and cultured ASM reaggregate preparations. The latter preparation results in the disruption of normal peripheral nervous ASM associations through enzymatic dissociation of cells.
  
  
  RESULTS
  We observed an increased level of depolarization in asthmatic preparations at the same level of exposure. Exposure to PbTx produced concentration-dependent depolarization in both nonasthmatic and asthmatic in vitro SPs. In the former, responses did not occur in the presence of the blocking agents such as atropine or tetrodotoxin (TTX). In asthmatic SPs, atropine and TTX produced little effect, whereas verapamil blocked the PbTx-induced depolarization. The toxin was without effect in nonasthmatic cultured cells, whereas acetylcholine produced depolarization that was blocked in the presence of atropine, but not TTX or verapamil. In contrast, the toxin produced significant depolarization in cultured asthmatic ASM cells, which were unaffected by either atropine or TTX but were blocked by verapamil.
  
  
  CONCLUSIONS
  We propose that PbTx directly affects asthmatic ASM whereas the effect is neurally mediated in nonasthmatics.
authors.affiliation: Department of Environmental and Occupational Health, University of South Florida College of Public Health, 13201 Bruce B. Downs Blvd., Tampa, FL 33612, USA. irichard@health.usf.edu
authors.forename: Ira S
authors.initials: IS
authors.lastname: Richards
authors.forename: Marie
authors.initials: M
authors.lastname: Bourgeois
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001285:Atropine / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008387:Marine Toxins / Q000008:administration & dosage / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D055815:Young Adult
chemical_list: C017885:Gymnodinium breve toxin; D008387:Marine Toxins; D013779:Tetrodotoxin; D001285:Atropine; D014700:Verapamil; D000109:Acetylcholine