Inhibition of end-plate desensitization by sodium

Parsons, R. L.; Schnitzler, Ronald M.; Cochrane, DE

doi:10.1152/ajplegacy.1974.227.1.96

Cited by 18 publications

(10 citation statements)

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“…This linearity has been reported by Harrington (1973) for the membrane voltage response, measured directly with microelectrodes, to agonist applied by microperfusion. It is difficult to determine the exact nature of the interaction between ACh and the receptor from this type of plot because of desensitization of the response (e.g., Parsons, Schnitzler, and Cochrane, 1974), possible shifts in intracellular C1-concentration (Jenkinson and Terrar, 1973), and the voltage dependency of the ACh-activated membrane conductance (Dionne and Stevens, 1975). The double reciprocal plot is, however, useful for estimating the maximum ACh-activated voltage response, AV,,,, from the reciprocal of the Y-axis intercept.…”

Section: Methodsmentioning

confidence: 99%

Permeability of the endplate membrane activated by acetylcholine to some organic cations

1977

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The ability of various organic cations to depolarize the ACh-activated endplate membrane in the absence of Na ions was examined on frog sartorius muscle by measuring the endplate potential on the muscle surface with the moving electrode technique. The ACh-activated endplate membrane was very permeable to ammonium and its methyl and hydroxy derivatives, and moderately permeable to guanidine derivatives and Tris (hydroxymethyl) aminomethane. The permeability of alkylol derivatives of ammonium diminished progressively with increase in molecular size. The present results suggested that the endplate ionic channels can be represented by a pore of about 6.4 A in diameter.

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Section: Methodsmentioning

confidence: 99%

Permeability of the endplate membrane activated by acetylcholine to some organic cations

1977

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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agent transports monovalent as well as divalent cations (Pressman, 1973;Devore & Nastuk, 1975;Schnitzler & Parsons, unpublished observations).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%

“…In the continued presence of recently that this site is located on the internal surface agonist, the conductance gradually returns toward the of the postjunctional membrane and therefore is pre-activation state as 'desensitization' occurs distinct from the agonist-recognition site on the (Thesleff, 1955). Manthey (1966) has shown that external surface of this membrane (Nastuk & Parsons, raising the external calcium concentration accelerates 1970; Cochrane & Parsons, 1972;Parsons, Schnitzler & Cochrane, 1974). This view would be greatly…”

Section: Introductionmentioning

confidence: 98%

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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“…In spite of the fact that our understanding of the molecular aspects of receptor-channel gating at the motor end-plate has increased markedly in recent years, the molecular mechanism responsible for the development of desensitization still remains obscure. There are a number of environmental factors such as membrane voltage, extracellular and intracellular ionic concentrations, and agonist concentration which can markedly alter the time course of onset of desensitization (Manthey, 1966;Magazanik & Vyskocil, 1970;Nastuk & Parsons, 1970;Parsons, Schnitzler & Cochrane, 1974; De Bassio, Parsons & Schnitzler, 1976;Parsons, 1978;Chestnut, 1983). The development of desensitization is particularly sensitive to the extent of receptor-channel activation.…”

Section: Introductionmentioning

confidence: 99%

Comparison of cholinergic activation and desensitization at snake twitch and slow muscle fibre end‐plates.

Connor¹,

Fiekers²,

Neel³

et al. 1984

The Journal of Physiology

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SUMMARY1. Characteristics of receptor-channel activation and desensitization have been compared at voltage-clamped snake slow and twitch fibre end-plates maintained in an isotonic potassium propionate solution.2. Miniature end-plate current (m.e.p.c.) decay was slower and less voltage dependent at slow fibre end-plates than at twitch fibre end-plates. The peak m.e.p.c. amplitude versus voltage relationship and reversal potential were similar at the two end-plate types.3. Acetylcholine-induced noise and m.e.p.c.s were recorded at slow fibre end-plates. At most slow fibres the spectral density was not adequately fitted by a single Lorentzian function. Rather, the observed spectral density was greater at high frequencies than the values predicted using the m.e.p.c. decay rate. The noise could be well described by the sum of two Lorentzian functions, one of which corresponded to a single Lorentzian function with the corner frequency determined by the m.e.p.c. decay rate.4. The shape of the carbachol concentration-peak end-plate current relationship was similar at both slow and twitch fibre end-plates. However, for all concentrations tested, the peak carbachol-induced end-plate current (e.p.c.carb ) value was markedly less at slow fibre end-plates than at twitch fibre end-plates. 5. The onset of desensitization was determined using two methods. The first concerned analysis of the time course of decay of the e.p.c.carb from a peak value during the sustained application of agonist. The second involved a double-perfusion technique in which a 'desensitizing' dose was applied for varying intervals before the application of a second 'test' dose of carbachol. With both methods the development of desensitization at both end-plate types was dependent on carbachol concentration and duration of exposure. At each end-plate type the time course of desensitization onset often exhibited two components; one with a time constant of seconds and a slower component having time constants in the range of tens to hundreds of seconds. E. A. CONNOR AND OTHERS6. The slope of the relationship between carbachol concentration and equilibrium desensitization at slow and twitch fibre end-plates was close to two, suggesting that two molecules of agonist are probably bound during the development of desensitization. However, for all concentrations tested, desensitization developed more rapidly and to a greater extent at twitch fibre end-plates than at slow fibre end-plates.7. The voltage dependence of the 3 min steady-state desensitization produced by 108 jSM-carbachol was very similar (--0.0250 mV-1) at both fibre types. However, the 3 min steady-state level of desensitization was consistently greater at corresponding voltages for twitch fibre end-plates than at slow fibre end-plates. It was also observed at twitch fibre end-plates exposed to 216,M-carbachol that the fast component of desensitization and 3 min steady-state level of desensitization could exhibit different voltage dependencies. This is consistent with the view that the fast and slow ...

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Inhibition of end-plate desensitization by sodium

Cited by 18 publications

References 0 publications

Permeability of the endplate membrane activated by acetylcholine to some organic cations

Permeability of the endplate membrane activated by acetylcholine to some organic cations

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

Comparison of cholinergic activation and desensitization at snake twitch and slow muscle fibre end‐plates.

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