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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Parsons, R. L. Hardwick, J. C. Coniglio, L. M. |
| Description | Author Affiliation: Hardwick JC ( Department of Anatomy & Neurobiology, University of Vermont College of Medicine, Burlington 05405.) |
| Abstract | 1. The effect of the protein kinase inhibitor, staurosporine, on the extent and time course of recovery following carbachol-induced desensitization was studied in snake twitch-muscle fibres maintained in an isotonic potassium propionate solution and voltage-clamped to +30 mV. 2. Pretreatment with staurosporine (0.5 microM) decreased the extent of recovery of spontaneous miniature endplate current (m.e.p.c.) amplitudes following desensitization by a sustained application of 540 microM carbachol. Recovery was inhibited by approximately 50% without altering the time course of m.e.p.c. recovery. 3. Staurosporine also produced a concentration-dependent (10 nM to 0.5 microM) decrease in the amplitude of a second carbachol-induced current, following a wash period, as compared to the amplitude of the current produced by the initial carbachol application. Pretreatment with 0.5 microM K252a, another wide spectrum protein kinase inhibitor, also decreased the extent of recovery of the response to a second carbachol application following desensitization. 4. Staurosporine pretreatment (0.5 microM) had no effect on either the kinetics of receptor-channel gating or the initial endplate sensitivity to agonist. This was determined by comparing the amplitude of the carbachol (540 microM)-induced currents and the amplitude and decay rate of m.e.p.cs in control and staurosporine-treated fibres. 5. Staurosporine had no effect on the time course of desensitization onset produced during the initial application of 540 microM carbachol or the depth of desensitization produced by the end of a 2-3 min exposure to 540 microM carbachol.6. Elevation of the external calcium concentration from 1 to 10mM during the 540 microM carbachol application completely antagonized the decreased extent of recovery of m.e.p.c. amplitude produced by pretreatment with 0.5 microM staurosporine.7. We suggest that phosphorylation of a population of acetylcholine receptors is required for complete recovery from desensitization, and that staurosporine inhibits the protein kinases responsible for this phosphorylation.8. We further propose that a transient increase in intracellular calcium, produced by an increase in calcium influx through agonist-activated endplate channels, stimulates additional protein kinase activity, which in turn, antagonizes the effect of staurosporine-treatment on recovery. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 104 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1991-12-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Alkaloids Pharmacology Carbachol Cholinergic Antagonists Muscle Contraction Drug Effects Muscles Physiology Animals Calcium Metabolism Electrophysiology Ion Channel Gating Motor Endplate Neuromuscular Depolarizing Agents Phosphorylation Protein Kinase C Antagonists & Inhibitors Protein Kinase Inhibitors Staurosporine Synapses Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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