Muscarinic effects of the Caribbean ciguatoxin C-CTX-1 on frog atrial heart muscle.
The effects of Caribbean ciguatoxin (C-CTX-1) isolated from horse-eye jack (Caranx latus) on the electrical and mechanical activities of frog auricle were studied. C-CTX-1 (1 pM-50 nM) dose-dependently shortened the duration of the plateau and the repolarizing phase of the action potential (AP). The AP shortening induced by C-CTX-1 (50 nM) was suppressed or prevented either by tetrodotoxin (TTX; 0.6 nM) or by atropine (0.1mM). C-CTX-1 (50 nM) prolonged the TTX (0.6 nM)-sensitive electrical response of the vagus nerve branches, which innervate the auricle. The C-CTX-1 (50 nM)-induced shortening of the plateau and of the repolarization phase were prevented or reversed by gallamine (20 microM) and pirenzepine (0.5 microM), respectively. C-CTX-1 (50 nM) decreased the amplitude of the peak contraction and shortened its duration. In the presence of gallamine (20 microM), C-CTX-1 decreased the amplitude of the peak contraction and shortened its duration in the presence of pirenzepine (0.5 microM). C-CTX-1 (50 nM) decreased the time constant of the relaxation phase of the peak contraction suggesting that it increased the Na(+)/Ca(2+) exchange activity. Acetylcholine (ACh; 1 pM) shortened APD, decreased the peak contraction and mimics the effects of C-CTX-1. In conclusion, the presented data show that C-CTX-1 released ACh from atrial cholinergic nerve terminals which activated M(1) and M(2) muscarinic receptors subtype (mAChR). Our findings suggest that M(1) and M(2) mAChR are present in frog atrial tissue and play a previously unrecognized role in the modulation of the AP duration and of the mechanical activity of cardiac tissue.
Sauviat
Martin-Pierre
MP
Laboratoire d'Optique et Biosciences, INSERM U 451, UMR CNRS 7645, Ecole Polytechnique-ENSTA, 91128, Palaiseau, France. martin-pierre.sauviat@polytechnique.fr
Marquais
Michel
M
Vernoux
Jean-Paul
JP
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002922:Ciguatoxins / Q000494:pharmacology*; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011893:Rana esculenta; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D002922:Ciguatoxins; D013779:Tetrodotoxin; D000109:Acetylcholine