The effect of (+)‐tubocurarine on neuromuscular transmission during repetitive stimulation in the rat, mouse, and frog.

Abstract

SUMMARY1. The effect of tubocurarine on amplitudes of end-plate currents in response to trains of repetitive stimulation (50-150/sec) was investigated in voltage-clamped muscle fibres of the rat, mouse and frog.2. In rat and mouse muscle, the presence of tubocurarine led to a more rapid decline (rundown) in the amplitudes of successive end-plate currents during trains of impulses. In frog, tubocurarine caused an increase in apparent facilitation of end-plate current amplitudes during the first few impulses of repetitive stimulation; this increase was followed by a more rapid rundown of end-plate current amplitude.3. These effects of tubocurarine appear not to be an artifact resulting from inadequate control of membrane potential in voltage-clamped fibres.4. The more rapid rundown during trains of end-plate currents in the presence of tubocurarine showed little variation with membrane potential indicating that voltage-sensitive channel blockade by tubocurarine was not a major factor contributing to the rundown.5. The effect oftubocurarine on the apparent facilitation and rundown ofend-plate current amplitudes was typically decreased by reducing the frequency of stimulation.6. These results suggest that tubocurarine affects transmitter release at neuromuscular junctions during repetitive stimulation.

Phenthonium, a quaternary derivative of (−)−hyoscyamine, enhances the spontaneous release of acetylcholine at rat motor nerve terminals

“…Equal concentrations of Phen did not alter the rundown of successively evoked e.p.ps as did tubocurarine (Figure 6). The faster rundown of the endplate current amplitudes recorded in the presence of tubocurarine have been attributed to its prejunctional actions (Glavinovic, 1979b;Magleby et al, 1981;. A faster decay of the e.p.p.…”

Pre‐and post‐junctional effects of tubocurarine and other nicotinic antagonists during repetitive stimulation in the rat.

“…train run-down in tubocurarine, Magleby et al (1981) concluded that the effect was not a consequence of channel block and must therefore be the result of a prejunctional action. To test this hypothesis, the effects of tubocurarine and trimetaphan were examined on trains of e.p.c.s evoked by repetitive (50 Hz) ionophoretic application of short pulses of ACh to the end-plate, and these effects were compared to their effects on trains of neurally evoked e.p.c.s.…”

“…Controversy has arisen as to whether the action of tubocurarine which leads to run-down of trains of e.p.p.s or e.p.c.s during repetitive stimulation may be prejunctional in origin (Blaber, 1970(Blaber, , 1973Hubbard & Wilson, 1973;Glavinovic, 1979b;Magleby, Pallotta & Terrar, 1981), or whether it represents a use-dependent block of the receptor-associated ion channel (Dreyer, 1982), of the type first suggested for tubocurarine by Manalis (1977) and Katz & Miledi (1978) and later comprehensively studied by Colquhoun, Dreyer & Sheridan (1979).…”

Multiple effects of α‐toxins on the nicotinic acetylcholine receptor

“…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].…”