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Titolo:
NECESSITY OF DIVALENT-CATIONS FOR RECOVERY FROM CARBACHOL-INDUCED NICOTINIC ACETYLCHOLINE-RECEPTOR INACTIVATION AT SNAKE TWITCH FIBER END-PLATES
Autore:
HARDWICK JC; PARSONS RL;
Indirizzi:
UNIV VERMONT,COLL MED,DEPT ANAT & NEUROBIOL BURLINGTON VT 05405
Titolo Testata:
British Journal of Pharmacology
fascicolo: 2, volume: 110, anno: 1993,
pagine: 889 - 895
SICI:
0007-1188(1993)110:2<889:NODFRF>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEUROMUSCULAR-JUNCTIONS; DESENSITIZATION; ACTIVATION; FIBERS;
Keywords:
ACETYLCHOLINE RECEPTORS; STAUROSPORINE; PROTEIN PHOSPHORYLATION; MINIATURE END-PLATE CURRENTS; SINGLE CHANNEL RECORDINGS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
15
Recensione:
Indirizzi per estratti:
Citazione:
J.C. Hardwick e R.L. Parsons, "NECESSITY OF DIVALENT-CATIONS FOR RECOVERY FROM CARBACHOL-INDUCED NICOTINIC ACETYLCHOLINE-RECEPTOR INACTIVATION AT SNAKE TWITCH FIBER END-PLATES", British Journal of Pharmacology, 110(2), 1993, pp. 889-895

Abstract

1 Previous studies demonstrated that elevation of the extracellular calcium concentration during a prolonged exposure to a high concentration of carbachol reverses the staurosporine-induced decrease in the extent of endplate resensitization in voltage-clamped snake twitch fibres. The present studies were designed to establish the site, specificityand potential mechanisms by which calcium could reverse the effects of staurosporine on acetylcholine receptor recovery. 2 Pretreatment of potassium-depolarized muscle preparations with 0.5 muM staurosporine, followed by a 10 min incubation with 540 muM carbachol, produced a significant decrease in the recovery of miniature endplate current (m.e.p.c.) amplitudes. Raising the extracellular calcium concentration from 1 mM to 10 mM during the agonist application reversed this inhibition. In addition, a brief (3 min) incubation in an elevated calcium (10 mM) solution in staurosporine-treated preparations previously exposed to540 muM carbachol also reversed the reduction in m.e.p.c. amplitude. 3 Substitution of calcium with 10 mM strontium had no effect on the staurosporine-induced decrease in m.e.p.c. amplitude, whereas 10 mM magnesium partially substituted for calcium. Inclusion of (+)-tubocurarine(13 muM) in the 10 mM calcium solution to prevent the influx of calcium through agonist-activated channels did not prevent the reversal of the staurosporine-induced decrease in m.e.p.c. amplitudes. This suggested that the site of action of calcium on endplate resensitization wasextracellular. 4 Analysis of acetylcholine (ACh)-induced single channel currents demonstrated that a population of small conductance channels seen only in the staurosporine-treated preparations following carbachol exposure, was still present in staurosporine-treated preparationsincubated in 540 muM carbachol solution containing 10 mM calcium. Thus the effect of calcium on ACh receptor recovery was not due to the conversion of the small conductance channels to the normal, large conductance channels. 5 Removal of calcium from the extracellular solution with the magnesium concentration unchanged, resulted in no change in the extent of m.e.p.c. amplitude recovery, nor did it alter the ability of staurosporine to inhibit recovery. Removal of both calcium and magnesium resulted in a significant decrease in the extent of recovery andstaurosporine produced no additional decrease. This decrease in m.e.p.c. recovery in the divalent cation-free solution was not associated with a change in mean channel conductance as determined by noise analysis. 6 Based on the results from these experiments, we suggest that, with prolonged exposure to agonist, some ACh receptors at the endplate become irreversibly inactivated. For full recovery of endplate sensitivity to occur, inactivated ACh receptors must be replaced. Part of the replacement ACh receptors appear to be recruited from a readily available but not previously activated pool and this process is dependent onextracellular calcium and/or magnesium. Thus, elevation of extracellular calcium may be able to reverse the apparent decrease in endplate sensitivity in staurosporine-treated fibres following carbachol exposure by increasing the number of functional receptors at the endplate.

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Documento generato il 01/12/20 alle ore 00:17:26