The m3 muscarinic acetylcholine receptor differentially regulates calcium influx and release through modulation of monovalent cation channels
| Autor: | Reed C. Carroll, Ernest G. Peralta |
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| Rok vydání: | 1998 |
| Předmět: |
Agonist
Carbachol Cations Divalent medicine.drug_class CHO Cells Pharmacology Biology Muscarinic agonist Ion Channels General Biochemistry Genetics and Molecular Biology Membrane Potentials Cricetinae Muscarinic acetylcholine receptor medicine Animals Receptor Molecular Biology Ion channel Receptor Muscarinic M3 Membrane potential Dose-Response Relationship Drug General Immunology and Microbiology General Neuroscience Depolarization Cations Monovalent Receptors Muscarinic Biophysics Calcium Ion Channel Gating Research Article Signal Transduction medicine.drug |
| Zdroj: | The EMBO Journal. 17:3036-3044 |
| ISSN: | 1460-2075 |
| DOI: | 10.1093/emboj/17.11.3036 |
| Popis: | Several types of transmembrane receptors regulate cellular responses through the activation of phospholipase C-mediated Ca2+ release from intracellular stores. In non-excitable cells, the initial Ca2+ release is typically followed by a prolonged Ca2+ influx phase that is important for the regulation of several Ca2+-sensitive responses. Here we describe an agonist concentration-dependent mechanism by which m3 muscarinic acetylcholine receptors (mAChRs) differentially regulate the magnitude of the release and influx components of a Ca2+ response. In transfected Chinese hamster ovary cells expressing m3 mAChRs, doses of the muscarinic agonist carbachol ranging from 100 nM to 1 mM evoked Ca2+ release responses of increasing magnitude; maximal Ca2+ release was elicited by the highest carbachol concentration. In contrast, Ca2+ influx was maximal when m3 mAChRs were activated by moderate doses (1-10 microM) of carbachol, but substantially reduced at higher agonist concentrations. Manipulation of the membrane potential revealed that the carbachol-induced Ca2+ influx phase was diminished at depolarized potentials. Importantly, carbachol doses above 10 microM were found to couple m3 mAChRs to the activation of an inward, monovalent cation current resulting in depolarization of the cell membrane and a selective decrease in the influx, but not release, component of the Ca2+ response. These studies demonstrate, in one experimental system, a mechanism by which a single subtype of G-protein-coupled receptor can utilize the information encoded in the concentration of an agonist to generate distinct intracellular Ca2+ signals. |
| Databáze: | OpenAIRE |
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