Nicotinic antagonists produce differing amounts of tetanic fade in the isolated diaphragm of the rat

Abstract

1 The effects of nicotine antagonists on single twitches, trains of four twitches and tetanic contractions of the isolated diaphragm of the rat were examined. 2 Different drugs were found to produce different amounts of tetanic fade relative to depression of twitch tension. 3 The order of activity from most able, to least able to produce fade was: hexamethonium>trimeta-phan = atracurium = tubocurarine > pancuronium > erabutoxin b. 4 The effect of erabutoxin b was distinctive for its almost complete lack of tetanic fade. 5 3, 4-Diaminopyridine increased tetanic fade produced by tubocurarine, atracurium and hexamethonium, but not that produced by erabutoxin b. 6 It is concluded that nicotinic antagonists act at more than one site at the neuromuscular junction. Assuming block of the postjunctional acetylcholine receptor produces tension depression, a second or third site must be involved in producing tetanic fade. 7 The possibility that tetanic fade results from block of the ion channel associated with the postjunctional acetycholine receptor or from the block of a prejunctional nicotinic receptor is discussed.

Multiple effects of α‐toxins on the nicotinic acetylcholine receptor

“…The fade increased significantly when a high concentration of or-toxin was rapidly reduced by washing out but the effects of ce-bungarotoxin were essentially unchanged after washout. These results confirm reports in the literature that ce-toxins do cause a fade [12] and do not cause a fade [5,6]. Our results show that these conflicting results can now be explained as a concentration-dependent effect.…”

“…The decrease in ACh release would result in fade because of the additional postsynaptic AChR block by curare. Here, we provide evidence that the a-toxin from N. naja atra does not produce much fade at high concentrations, which supports the findings of others [5,6,9,10]. However, it was found that very low concentrations of a,-toxin (< 10 nM) did produce a dramatic fade which was identical to the effects of curare.…”

“…Others have suggested that the binding site involved in the production of fade could be a presynaptic AChR [2][3][4][5][6][7][8]. In evaluation of our data it is important to underscore the fact that all efforts to detect interaction or binding of o~-toxins to putative presynaptic ACh receptors of any type have been unsuccessful [11].…”

“…Reports that or-toxins do not cause fade as does curare [5,6,9,10] and do not bind to the presynaptic nerve terminal [11] have been cited as support for this theory [2,5,9]. It has been reported that unlike curare, the or-toxin from Laticauda semifasciata does not cause a fade in end-plate currents [5], nor does it bring about tetanic fade in the isolated rat diaphragm [6]. Similarly, it has been reported that a,-bungarotoxin from Bungarus multicinctus does not cause tetanic fade in the tibialis anterior muscle of the anaesthetized cat [9,10].…”

“…It has been proposed that fade is caused in part by a presynaptic effect of curare [2][3][4][5][6][7][8]. Reports that or-toxins do not cause fade as does curare [5,6,9,10] and do not bind to the presynaptic nerve terminal [11] have been cited as support for this theory [2,5,9]. It has been reported that unlike curare, the or-toxin from Laticauda semifasciata does not cause a fade in end-plate currents [5], nor does it bring about tetanic fade in the isolated rat diaphragm [6].…”