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Titolo:
NECESSITY OF PROTEIN-KINASE-C ACTIVITY FOR MAINTENANCE OF ACETYLCHOLINE-RECEPTOR FUNCTION AT SNAKE TWITCH FIBER END-PLATES
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: 433 - 441
SICI:
0007-1188(1995)114:2<433:NOPAFM>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
STAUROSPORINE; DESENSITIZATION; INHIBITOR; RECOVERY; CHANNEL; CELLS; FIBERS; POTENT;
Keywords:
SINGLE CHANNELS; STAUROSPORINE; MEPCS; SNAKE TWITCH FIBER END-PLATES; ACETYLCHOLINE RECEPTORS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
J.C. Hardwick e R.L. Parsons, "NECESSITY OF PROTEIN-KINASE-C ACTIVITY FOR MAINTENANCE OF ACETYLCHOLINE-RECEPTOR FUNCTION AT SNAKE TWITCH FIBER END-PLATES", British Journal of Pharmacology, 114(2), 1995, pp. 433-441

Abstract

1 The extent of recovery of endplate sensitivity following a 5 or 10 min exposure to carbachol was determined from measurements of miniature endplate current (m.e.p.c.) amplitudes in voltage-clamped snake twitch fibre endplates. M.e.p.c. amplitude recovery was dependent on the carbachol concentration (0.27-5.4 mM) and duration of application. Staurosporine pretreatment (0.5 mu M for similar to 15 min) further decreased the extent of m.e.p.c. amplitude recovery. 2 The decrease in m.e.p.c. amplitude at control endplates exposed to high concentrations of agonist (5.4 mM carbachol for 10 min) was due to an apparent decrease in postsynaptic receptor density, not to a change in the conductance ofthe acetylcholine (ACh)-activated channels. 3 Pretreatment with either 1 mu M lavendustin A or 50 mu M KN-62 had no effect on m.e.p.c. amplitude recovery, whereas pretreatment with either 0.5 mu M staurosporine, 50 mu M sphingosine, or 0.5 mu M calphostin C significantly reducedm.e.p.c. amplitude recovery following carbachol exposure. 4 Sphingosine and staurosporine produced a concentration-dependent decrease in the extent of m.e.p.c. amplitude recovery, but had no effect on m.e.p.c.characteristics in the absence of carbachol. In addition, this decrease in m.e.p.c. amplitude was not due to the presence of a subpopulation of small amplitude m.e.p.cs. 5 Prolonged treatment (18-20 h) of muscles with 200 nM phorbol 12-myristate 13-acetate (PMA), to down regulate protein kinase C, resulted in a significant reduction in m.e.p.c. amplitudes following exposure to carbachol. Conversely, treatment with 200 nM 4 alpha PMA, an inactive analogue, had no effect on m.e.p.c. amplitude recovery. 6 Only large amplitude ACh-activated channels (similar to 50 pS) were recorded from fibres either in the presence of 50 mu M sphingosine or from fibres chronically exposed to PMA. However, following recovery from a 10 min exposure to 540 mu M carbachol, both small conductance (similar to 25 pS) and large conductance ACh-activated channels were recorded in both sphingosine- and phorbol-treated preparations. The conductance of these two populations of channels was virtually identical to those seen in staurosporine-treated fibres following carbachol exposure. 7 We conclude that protein kinase C is required for'full recovery of AChR sensitivity following carbachol-induced receptor inactivation. Exposure to high concentrations of agonist for prolonged periods appears to result in the inactivation of a subpopulation of receptors. These receptors must be replaced or reactivated by a process involving protein kinase C. When this phosphorylation step is inhibited, the AChRs remain in an activatable form, but with a reduced conductance.

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Documento generato il 25/11/20 alle ore 01:02:44