The interactions of α-bungarotoxin or tubocurarine with the neuromuscular block and endplate depolarization induced by succinylcholine (SCh) in the phrenic nerve-diaphragm preparation of mice were studied in order to elucidate the role of depolarization by SCh in the neuromuscular blockade. The SCh concentrations required to depress the indirect twitch response by 20% and the evoked endplate potential in cut muscle preparations by 80% were 10 μM and 6 μM, respectively, while only 2 μM SCh was needed to induce maximal endplate depolarization from -80 mV to about -60 mV. SCh blocked the neuromuscular transmission synergistically with either α-bungarotoxin or tubocurarine. There was an initial partial reversal of the neuromuscular inhibition caused by tubocurarine, but not that by α-bungarotoxin. α-Bungarotoxin (0.025 μM) antagonized SCh (10 μM)-induced depolarization more effectively than it depressed miniature endplate potentials and the antagonism was insurmountable by increasing SCh concentration. By contrast, tubocurarine preferentially depressed miniature endplate potentials and antagonized SCh-depolarizaztion competitively. The above difference was attributed to the irreversible nature of α-bungarotoxin binding to acetylcholine receptors, to the slow diffusion of the toxin molecule into the synaptic cleft and thus to the more rapid binding with perijunctional receptors compared with junctional ones. It is concluded that the sustained depolarization of the endplate by SCh results largely from an action on the perijunctional receptor in mice and, unlike cats, the neuromuscular bock by SCh is not due to the depolarization per se but rather to a direct attenuation of endplate potential.
|Number of pages||7|
|Journal||British Journal of Pharmacology|
|Publication status||Published - 1989|
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