Specificity of Coupling of Muscarinic Receptor Isoforms to a Novel Chick Inward-rectifying Acetylcholine-sensitive K+ Channel
Autor: | Steven C. Hebert, Daniela Riccardi, Jonas B. Galper, Leeying Wu, Albert P. Gadbut |
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Rok vydání: | 1996 |
Předmět: |
medicine.medical_specialty
Potassium Channels Molecular Sequence Data Xenopus Chick Embryo In Vitro Techniques Pertussis toxin Biochemistry Xenopus laevis Internal medicine M current Muscarinic acetylcholine receptor medicine Animals Tissue Distribution Channel blocker Amino Acid Sequence RNA Messenger Cloning Molecular Potassium Channels Inwardly Rectifying Molecular Biology Sequence Homology Amino Acid biology Brain Muscarinic acetylcholine receptor M3 Cell Biology biology.organism_classification Receptors Muscarinic Molecular biology Acetylcholine Rats Coupling (electronics) Endocrinology G Protein-Coupled Inwardly-Rectifying Potassium Channels Female Chickens medicine.drug |
Zdroj: | Journal of Biological Chemistry. 271:6398-6402 |
ISSN: | 0021-9258 |
Popis: | The G-protein-gated inward-rectifying K+ channel GIRK1 has been demonstrated in heart and brain. These tissues also both express the M2, M3, and M4, muscarinic acetylcholine receptors (mAChR) (Gadbut, A.P., and Galper, J.B. (1994),J. Biol. Chem. 269,25823-25829). Only the M2 mAChR has been demonstrated to couple to GIRK1 (Kubo, Y., Reuveny, E., Slesinger, P. A., Jan, Y. N., and Jan, L. Y. (1993) Nature 264, 802-806). In this study we determined the specificity of coupling of the M3 and M4 mAChR to a new GIRK1 cloned from a chick brain cDNA library. This clone codes for a 492-amino acid protein that is 93% identical to rat GIRK1 and is expressed in brain, atrium, and ventricle, but not skeletal muscle. In Xenopus laetis oocytes co-expression of GIRK1 with either the chick M2 or M4 mAChR gave carbamylcholine (10 microm)-stimulated K+ currents of 308 +/-26 nA and 298 +/-29 nA, respectively, which were both Ba2+- and pertussis toxin-sensitive. Activation of the M3 receptor produced 2382 +/-478 nA of current which was insensitive to Ba2+ and pertussis toxin, but was 85% inhabitable by the Cl channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (10-20 microm) consistent with coupling to an endogenous Ca2+-activated Cl- channel via a phosphatidylinositol-dependent mechanism. Co-expression of the cardiac inward rectifier CIR with chick M2 or M4 mAChR and GIRK1 increased currents more than 10-fold, but had no effect on specificity of coupling. These data demonstrate a new function for the M4 mAChR and a high degree of specificity for coupling of each receptor subtype to GIRK1. |
Databáze: | OpenAIRE |
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