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Titolo:
REQUIREMENT OF A COLCHICINE-SENSITIVE COMPONENT OF THE CYTOSKELETON FOR ACETYLCHOLINE-RECEPTOR RECOVERY
Autore:
HARDWICK JC; PARSONS RL;
Indirizzi:
UNIV VERMONT,COLL MED,DEPT ANAT & NEUROBIOL BURLINGTON VT 05405 UNIV VERMONT,COLL MED,DEPT ANAT & NEUROBIOL BURLINGTON VT 05405
Titolo Testata:
British Journal of Pharmacology
fascicolo: 2, volume: 114, anno: 1995,
pagine: 442 - 446
SICI:
0007-1188(1995)114:2<442:ROACCO>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
SKELETAL-MUSCLE; SNAKE TWITCH; CHANNEL ACTIVITY; PHORBOL ESTER; PROTEIN; TORPEDO; DESENSITIZATION; PHOSPHORYLATION; CLUSTERS; FIBER;
Keywords:
STAUROSPORINE; MEPCS; SINGLE CHANNELS; COLCHICINE; ACH RECEPTORS; SNAKE TWITCH FIBER END-PLATES; CYTOSKELETON;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
J.C. Hardwick e R.L. Parsons, "REQUIREMENT OF A COLCHICINE-SENSITIVE COMPONENT OF THE CYTOSKELETON FOR ACETYLCHOLINE-RECEPTOR RECOVERY", British Journal of Pharmacology, 114(2), 1995, pp. 442-446

Abstract

1 The effect of colchicine treatment on acetylcholine receptor function was examined in potassium depolarized, voltage-clamped snake twitchfibre endplates. Receptor function was assessed by analysis of miniature endplate currents (m.e.p.c.) as well as acetylcholine (ACh)-induced single channel currents. 2 Pretreatment of snake muscle fibres with colchicine (10 mu M to 100 mu M) for 16-18 h had no effect on m.e.p.c.amplitude or decay rates. At higher concentrations (1 mM), there was a slight decrease in the average m.e.p.c. amplitude. 3 Colchicine produced a concentration-dependent decrease in the extent of m.e.p.c. amplitude recovery following a 10 min exposure to 540 mu M carbachol. Exposure of 100 mu M colchicine-treated preparations to 0.5 mu M staurosporine further reduced the extent of m.e.p.c. amplitude recovery following carbachol exposure. 4 The decrease in m.e.p.c. amplitude following carbachol exposure was not due to a shift in the m.e.p.c. reversal potential. In addition, the distribution of m.e.p.c. amplitudes remained unimodal in both control and colchicine (100 mu M)-treated preparations following carbachol exposure. 5 In addition to the normal, large conductance (similar to 48 pS) ACh-activated channels, a population of small conductance (similar to 29pS) channels was observed in colchicine-treated preparations following exposure to carbachol. In preparations treated with both colchicine and staurosporine and then exposed to carbachol, the conductance of these small channels was identical to that of colchicine or staurosporine alone. 6 We suggest that prolonged exposure of snake twitch fibre endplates to agonist results in the activation and desensitization of ACh receptors. Furthermore, we propose thatfor a subpopulation of the inactivated receptors, restoration of function requires both the integrity of a subsynaptic cytoskeletal component and phosphorylation by a staurosporine-sensitive protein kinase. One plausible mechanism is that some receptors become destabilized in the membrane and phosphorylation of a cytoskeletal component, whose distribution may depend on an intact microtubular system, is required to re-anchor these receptors. If this anchoring process is inhibited either by disruption of the cytoskeleton with colchicine, or inhibition of the kinase by staurosporine, these receptors remain activatable, but have a conductance.

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Documento generato il 01/12/20 alle ore 22:32:37