Characteristics of postjunctional carbamylcholine receptor activation and inhibition

Johnson, E.; Parsons, R. L.

doi:10.1152/ajplegacy.1972.222.3.793

Cited by 14 publications

(6 citation statements)

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“…In addition, X-537A rapidly depolarizes muscle fibres maintained in normal sodium Ringer solution presumably because this agent transports monovalent as well as divalent cations (Pressman, 1973;Devore & Nastuk, 1975;Schnitzler & Parsons, unpublished observations). As desensitization rate is influenced both by membrane potential (Magazanik & Vyskocil, 1970) and by intracellular sodium (Manthey, 1966;Parsons et al, 1974) (Manthey, 1966;Johnson & Parsons, 1972). The junctional region of individual muscle fibres was (Nastuk & Parsons, 1970;Manthey, 1972).…”

Section: General Methodsmentioning

confidence: 99%

Effect of Ionophore X‐537a on Desensitization Rate and Tension Development in Potassium‐depolarized Muscle Fibres

DeBassio

Parsons

Schnitzler

1976

British J Pharmacology

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I The effects of the ionophore X-537A were studied on carbamylcholine (carbachol)-induced desensitization and on tension development in relaxed potassium-depolarized frog sartorius muscles. 2 X-537A accelerated carbachol-induced desensitization in Ca2+-deficient solutions without having any effect on the conductance of the membrane in the absence of carbachol or on the extent of the carbachol-induced increase in conductance. 3 In Ca2+-deficient solution, the acceleration of desensitization by the ionophore was concentrationdependent. No effect was observed with concentrations less than 5,M and maximal acceleration was evident with 10 gM. 4 The influence of X-537A on desensitization was time-dependent. At 20 AM X-537A, there was a marked acceleration of desensitization by the end of 5 min exposure. An additional gradual acceleration occurred during a 5 to 30 min treatment. No acceleration of desensitization was evident when X-537A was simultaneously applied with carbachol to the end-plate region without prior exposure to the ionophore. 5 Desensitization also was accelerated by 30 min exposure to 20 gM X-537A in solutions containing Ca2+ or deficient in both Mg2+ and Ca2+; the rate being increased 2.8-fold in Ca2+-containing solutions, 2.9-fold in Ca2+-deficient solutions containing Mg2+, and 2.5-fold in divalent cation-deficient solutions. 6 Tension development gradually occurred in relaxed potassium-depolarized muscle preparations exposed to 20 gM X-537A. The onset of tension development occurred only after approximately 25 min of exposure both in preparations kept in Ca2+-deficient or Ca2+-containing solutions. By the end of 90 min in the ionophore, the tension developed was approximately 12% and 23% of the initial potassium contracture in those preparations maintained in the Ca2+-deficient or Ca2+-containing solutions, respectively. 7 We assume that the increase in desensitization rate following exposure to X-537A results from an elevation of the intracellular Ca2+ concentration. That muscle tension gradually increased during exposure to the ionophore supports this conclusion. The acceleration of desensitization by X-537A in the absence of external Ca2+ supports the view that the site of calcium acceleration is not on the external surface of the end-plate membrane either at or near the agonist-recognition site but rather on the inner surface.

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Section: General Methodsmentioning

confidence: 99%

Effect of Ionophore X‐537a on Desensitization Rate and Tension Development in Potassium‐depolarized Muscle Fibres

DeBassio

Parsons

Schnitzler

1976

British J Pharmacology

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“…For direct muscle stimulation, the preparation was first paralysed by the addition of a-bungarotoxin (2.5 yg ml-1). Direct (Manthey, 1966;Johnson & Parsons, 1972). In order to record e.p.ps in the absence of muscle contraction, preparations were paralysed by a high magnesium (8 mM), low calcium (0.9 mM) solution, or by addition of tubocurarine (4 x 10-6 M) to the bathing solution.…”

Section: Skeletal Muscle Preparationsmentioning

confidence: 99%

A further study of the neuromuscular effects of vesamicol (AH5183) and of its enantiomer specificity

Estrella

Green

Prior

et al. 1988

British J Pharmacology

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1 The effects of vesamicol (244-phenylpiperidino) cyclohexanol), an inhibitor of acetylcholine storage, and its two optical isomers have been studied on neuromuscular transmission in rat and frog muscle, and on nerve conduction in frog nerve. 2 Racemic vesamicol produced a pre-block augmentation of twitch tension that also occurred in directly-stimulated muscle. This effect is thus at least partially due to an increase in muscle contractility. 3 (-)-Vesamicol was approximately 20 times more potent than (+)-vesamicol in blocking twitches elicited at 1 Hz. This degree of stereoselectivity is similar to that measured for inhibition of acetylcholine-uptake by isolated synaptic vesicles. Both enantiomers were equally weak in reducing nerve action potential amplitude in frog nerve. 4 Further studies with the active isomer, (-)-vesamicol, showed that, like that produced by racemic vesamicol, the neuromuscular block was highly frequency-dependent. The block was not reversed by choline or neostiginine, but was partially reversed by 4-or 3,4-aminopyridine. 5 Preliminary electrophysiological studies showed that vesamicol reduced miniature endplate potential amplitude in rapidly-stimulated frog nerve-muscle preparations. Addition of lanthanum ions increased the frequency of miniature endplate potentials and led to the appearance of apparently normal-sized potentials amongst those of reduced amplitude. 6 The results show the close agreement between pharmacological and biochemical observations indicating the suitability of the rat diaphragm as a test model for substances of this nature. The degree of reversibility of the vesamicol-induced neuromuscular block by aminopyridines was unexpected, and it is suggested that in the presence of a drug which greatly increases release, a pool of acetylcholine is capable of being released which is not normally releasable after block of storage by vesamicol. It is also considered possible that the results from the intracellular recording studies may be explained in these terms.

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“…In frog muscle carbachol can produce depolarization to -17 mV (Johnson & Parsons, 1972). Decamethonium 1 /SM, which is a subthreshold concentration, produced depolarization to -42 mV in isolated cat muscle (Zaimis & Head, 1976, Fig.…”

Section: Limited Depolarization In Rat Musclementioning

confidence: 99%

Spontaneous recovery from depolarizing drugs in rat diaphragm.

Creese¹,

Mitchell²

1981

The Journal of Physiology

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SUMMARY1. The end-plate region in surface fibres of rat diaphragm was located by the use of polarizing filters.2. Carbachol (100,M) produced depolarization at the end-plate to -55 mV, as shown by continuous recording, with some indication of spontaneous recovery in the presence of the drug. The miniature end-plate potentials disappeared and remained absent.3. By repeated sampling it was found that the resting potential at the end-plate had largely recovered after 45 min in the presence of carbachol. Individual fibres showed much variation in the rate of recovery, and in some fibres the repolarization was rapid.4. In the absence of K, carbachol produced depolarization at the end-plate without significant recovery, as shown by repeated sampling.5. When muscles were exposed to ouabain (100 IaM) in addition to carbachol the end-plate remained depolarized without recovery for 60 min. The effect of ouabain was reversible: withdrawal of ouabain (in the presence of carbachol) led to substantial recovery.6. Suberyldicholine (100 /LM) gave results which were similar to those produced by carbachol.7. It was inferred that the spontaneous recovery of membrane potential in the presence of carbachol and of suberyldicholine is a process which is sensitive to K and to ouabain.

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Characteristics of postjunctional carbamylcholine receptor activation and inhibition

Cited by 14 publications

References 0 publications

Effect of Ionophore X‐537a on Desensitization Rate and Tension Development in Potassium‐depolarized Muscle Fibres

Effect of Ionophore X‐537a on Desensitization Rate and Tension Development in Potassium‐depolarized Muscle Fibres

A further study of the neuromuscular effects of vesamicol (AH5183) and of its enantiomer specificity

Spontaneous recovery from depolarizing drugs in rat diaphragm.

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