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Title: Muscarinic M1 receptor activation reduces maximum upstroke velocity of action potential in mouse right atria. Author: Islam MA, Nojima H, Kimura I. Journal: Eur J Pharmacol; 1998 Apr 10; 346(2-3):227-36. PubMed ID: 9652364. Abstract: We investigated whether acetylcholine affects cardiac action potentials through the muscarinic M1 in addition to M2 receptors in spontaneously beating mouse isolated right atria. A conventional glass microelectrode technique was used for the purpose. Acetylcholine (3-10 microM) reduced the maximum upstroke velocity of the action potentials (Vmax), followed by an increase. It shortened action potential duration at 90% repolarization, hyperpolarized the resting membrane and decreased the rate of beating. Atropine (3-100 nM) concentration dependently antagonized these effects of acetylcholine. Pirenzepine (10 and 30 nM), a selective muscarinic M1 receptor antagonist, antagonized acetylcholine (5 microM)-induced reduction of Vmax without affecting other effects of acetylcholine. In addition, pirenzepine (30 nM) induced an immediate and linear acceleration of the VmaX reduced by acetylcholine. In contrast, AF-DX 116 (11(¿2-[(diethylamino)-methyl]-1-piperidyl¿acetyl)-5,11-dihydro-6 H-pyridol[2,3-b][1,4]benzodiazepine-6-one base, 30-300 nM), a selective muscarinic M2 receptor antagonist, failed to antagonize acetylcholine-induced reduction of Vmax, but abolished its increase. It antagonized the shortening of action potential duration, membrane hyperpolarization and decreased the beating rate. McN-A-343 (4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium chloride, 100 and 300 microM), a muscarinic M1 receptor agonist, reduced Vmax and prolonged action potential duration, while oxotremorine (100-300 nM), a muscarinic M2 receptor agonist, evoked reverse effects. These results suggest that acetylcholine exerts a mixed effect on Vmax, consisting of a reduction and a facilitation, possibly mediated by concurrent activation of muscarinic M1 and M2 receptors, respectively, in isolated right atria of mice.[Abstract] [Full Text] [Related] [New Search]