Muscarinic effects of the Caribbean ciguatoxin C-CTX-1 on frog atrial heart muscle

摘要

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 (0.1 mM). 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 muM) and pirenzepine (0.5 muM), respectively. C-CTX-1 (50 nM) decreased the amplitude of the peak contraction and shortened its duration. In the presence of gallamine (20 muM), C-CTX-1 decreased the amplitude of the peak contraction and shortened its duration in the presence of pirenzepine (0.5 muM). C-CTX-1 (50 nM) decreased the time constant of the relaxation phase of the peak contraction suggesting that it increased the Na+/Ca2+ 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, and M2 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.