The relationship between stimulus‐induced antidromic firing and twitch potentiation produced by paraoxon in rat phrenic nerve‐diaphragm preparations

Clark, Amanda; Hobbiger, F.; Terrar, D A

doi:10.1111/j.1476-5381.1983.tb11044.x

Cited by 13 publications

(17 citation statements)

References 24 publications

(26 reference statements)

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“…Under certain conditions, the potentiation is also associated with repetitive antidromic nerve action potentials (Masland & Wigton, 1940;Feng & Li, 1941). Antidromic firing might thus be a mechanism for twitch potentiation but it cannot be the only mechanism since when antidromic firing is abolished by the disulphide bond reducing agent, dithiothreitol, peak twitch potentiation can be either unaffected or only slightly reduced (Clark, Hobbiger & Terrar, 1979,1983. A reduction in antidromic firing with little influence on twitch potentiation can also be obtained by varying the concentrations of Ca and Mg in the solution bathing the muscle (Clark, Hobbiger & Terrar, 1979, 1983.…”

Section: Introductionmentioning

confidence: 99%

Nature of the anticholinesterase‐induced repetitive response of rat and mouse striated muscle to single nerve stimuli.

Clark¹,

Hobbiger²,

Terrar³

1984

The Journal of Physiology

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SUMMARY1. The action of the anticholinesterase Paraoxon on neuromuscular transmission in rat diaphragm and mouse omohyoideus preparations was investigated.2. In both preparations, when Paraoxon potentiated the twitch in response to a single nerve stimulus, repetitive muscle action potentials were recorded with an intracellular electrode placed at the motor end-plate region.3. At end-plates of Paraoxon-treated rat diaphragm preparations where the membrane potential was not sufficiently negative to support muscle action potentials, repetitive end-plate potentials were recorded in response to a single nerve stimulus. No repetitive end-plate potentials could be recorded under such conditions in preparations which had been exposed to dithiothreitol before being treated with Paraoxon, although twitch potentiation and repetitive muscle action potentials were still observed in these preparations.4. In Paraoxon-treated mouse omohyoideus preparations only single end-plate potentials were recorded from end-plates where the membrane potential was not sufficiently negative to support muscle action potentials. This applied whether or not the preparation had been treated with dithiothreitol before being exposed to Paraoxon.5. In voltage-clamped rat diaphragm preparations which had been treated with Paraoxon, repetitive end-plate currents were frequently recorded in response to a single nerve stimulus. Under the same conditions mouse omohyoideus preparations responded with a single end-plate current.6. It is concluded that Paraoxon-induced twitch potentiation in rat diaphragm and mouse omohyoideus preparations is caused by repetitive muscle action potentials being triggered by a single nerve stimulus. Under the conditions stated, the repetitive muscle action potentials in rat diaphragm preparations arose from a prolonged end-plate potential or repetitive end-plate potentials or a combination of both. In mouse omohyoideus preparations the repetitive muscle potentials were the consequence of a single prolonged end-plate potential.

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Section: Introductionmentioning

confidence: 99%

Nature of the anticholinesterase‐induced repetitive response of rat and mouse striated muscle to single nerve stimuli.

Clark¹,

Hobbiger²,

Terrar³

1984

The Journal of Physiology

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“…It is thus possible that a fortuitous choice of doses and timing of their administration might also account at least in part for the observations of Webb & Bowman (1974). We have also shown previously (Clark, Hobbiger & Terrar, 1979, 1983 that, under certain conditions, twitch potentiation can be sustained in the absence of ADF. Reduction in ADF by hexamethonium therefore does not need to be associated with any reduction in twitch potentiation.…”

Section: Discussionmentioning

confidence: 69%

“…One chamber contained the muscle for tension recording and the other contained the phrenic nerve for recording ADF (Clark et al, 1979;1983). In the absence of paraoxon, a single stimulus applied to the nerve produced a single muscle twitch and a single antidromically conducted action potential (AP).…”

Section: Antidromic Firingmentioning

confidence: 99%

“…It has previously been observed (Clark, Hobbiger & Terrar, 1979;1983) that dithiothreitol (DTT), a disulphide bond reducing agent which re-C The Macmillan Press Ltd 1983 duces the affinity of ACh for nicotinic cholinoceptors at motor endplates (Terrar, 1978), abolishes paraoxon-induced ADF but not twitch potentiation. This paper also includes data on the effects of pancuronium and hexamethonium in DTT-treated preparations.…”

Section: Introductionmentioning

confidence: 99%

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Effects of pancuronium and hexamethonium on paraoxon‐induced twitch potentiation and antidromic firing in rat phrenic nerve diaphragm preparations

Clark

Hobbiger

Terrar

1983

British J Pharmacology

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1The actions of pancuronium, a selective antagonist of acetylcholine (ACh) at nicotinic cholinoceptors at motor endplates, and hexamethonium, a selective antagonist of ACh at nicotinic cholinoceptors in autonomic ganglia, have been studied in rat phrenic nerve diaphragm preparations. The effects on paraoxon-induced twitch potentiation and antidromic firing (ADF) in the phrenic nerve, were compared with the effects on normal twitch tension and intracellularly recorded miniature endplate potentials (m.e.p.ps) and endplate potentials (e.p.ps.) 2 In preparations exposed to paraoxon, pancuronium was found to be approximately 10 times more effective in reducing the potentiated component of the twitch than the component which corresponded to the pre-paraoxon twitch. A similar result was obtained with hexamethonium. 3 Pancuronium and hexamethonium, in concentrations which reduced paraoxon-induced twitch potentiation but had no effect on the twitch tension of preparations not treated with paraoxon, reduced paraoxon-induced ADF. The lowest concentrations of pancuronium and hexamethonium required for this also reduced the amplitude of m.e.p.ps and e.p.ps. 4 Dithiothreitol, a disulphide bond reducing agent which reduces the affinity of ACh for nicotinic cholinoceptors, enhanced the potency of pancuronium 2 to 3 fold. The same also applied for hexamethonium. 5 It is concluded that the experiments failed to provide evidence for an action of ACh on prejunctional nicotinic cholinoceptors of the ganglionic-type being involved in the initiation by paraoxon of twitch potentiation and ADF. Furthermore, the results obtained can be explained by pancuronium and hexamethonium reducing the action of ACh at the postjunctional membrane.

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“…BOT is regarded as a specific blocker of synaptic transmission at the neuromuscular junction and certain other cholinergic synapses (review Simpson, 1981). The mode of action of this toxin is thought to be at the level of the exocytosis of ACh quanta (Cull-Candy et al 1976; Kao et al 1976;Pumplin & Reese, 1977;Simpson, 1981 Randic & Straughan (1964) and Clark et al (1983). The levels of s.a.d.a.…”

Section: Discussionmentioning

confidence: 99%

Botulinum toxin prevents stimulus‐induced backfiring produced by neostigmine in the mouse phrenic nerve‐diaphragm.

Aizenman¹,

Bierkamper²,

Stanley³

1986

The Journal of Physiology

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SUMMARY1. The origin of motor nerve antidromic activity (backfiring) induced by anticholinesterase treatment was examined in the mouse phrenic nerve-hemidiaphragm preparation. Botulinum toxin was used to determine whether backfiring is due to (a) a direct effect of the cholinesterase inhibitor on the nerve terminal, or (b) an indirect effect via the prolongation of the action of acetylcholine.2. In previously untreated control preparations, neostigmine produced spontaneous and stimulus-induced antidromic activity in the phrenic nerve when rapidly introduced into the diaphragm via its vasculature. This activity could be reversibly blocked by d-tubocurarine and decamethonium, but not by atropine.3. Neostigmine-induced backfiring did not occur in preparations in which transmitter release was blocked with botulinum toxin.4. Infusion of a small bolus of a high concentration of acetylcholine following neostigmine treatment resulted in a short-term increase in the incidence of antidromic activity, followed by block, in both controls and botulinum toxin-treated preparations.5. It is concluded that transmitter release is necessary for the production of backfiring following cholinesterase inhibition since neostigmine alone does not elicit antidromic activity in botulinum toxin-treated preparations at concentrations which are effective in controls. Our results support the hypothesis that the effects of neostigmine on the motoneurone terminal are mediated by the prolonged action of acetylcholine that occurs with inhibition of acetylcholinesterase.

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The relationship between stimulus‐induced antidromic firing and twitch potentiation produced by paraoxon in rat phrenic nerve‐diaphragm preparations

Cited by 13 publications

References 24 publications

Nature of the anticholinesterase‐induced repetitive response of rat and mouse striated muscle to single nerve stimuli.

Nature of the anticholinesterase‐induced repetitive response of rat and mouse striated muscle to single nerve stimuli.

Effects of pancuronium and hexamethonium on paraoxon‐induced twitch potentiation and antidromic firing in rat phrenic nerve diaphragm preparations

Botulinum toxin prevents stimulus‐induced backfiring produced by neostigmine in the mouse phrenic nerve‐diaphragm.

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