title: M3 cholinoreceptors alter electrical activity of rat left atrium via suppression of L-type Ca2+current without affecting K+conductance.
abstract: Electrophysiological effects produced by selective activation of M3 cholinoreceptors were studied in isolated left atrium preparations from rat using the standard sharp glass microelectrode technique. The stimulation of M3 receptors was obtained by application of muscarinic agonist pilocarpine (10-5M) in the presence of selective M2 antagonist methoctramine (10-7M). Stimulation of M3 receptors induced marked reduction of action potential duration by 14.4 ± 2.4% and 16.1 ± 2.5% of control duration measured at 50 and 90% of repolarization, respectively. This effect was completely abolished by selective M3 blocker 4-DAMP (10-8M). In isolated myocytes obtained from the rat left atrium, similar pharmacological stimulation of M3 receptors led to suppression of peak L-type calcium current by 13.9 ± 2.6% of control amplitude (measured at +10 mV), but failed to affect K+currents Ito, IKur, and IKir. In the absence of M2 blocker methoctramine, pilocarpine (10-5M) produced stronger attenuation of ICaLand induced an increase in IKir. This additive inward rectifier current could be abolished by highly selective blocker of Kir3.1/3.4 channels tertiapin-Q (10-6M) and therefore was identified as IKACh. Thus, in the rat atrial myocardium activation of M3 receptors leads to shortening of action potentials via suppression of ICaL, but does not enhance the major potassium currents involved in repolarization. Joint stimulation of M2 and M3 receptors produces stronger action potential shortening due to M2-mediated activation of IKACh.
authors.affiliation: Department of Human and Animal Physiology, Biological Faculty of the Moscow State University, Leninskiye Gory, 1, 12, Moscow, Russia.
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Filatova
authors.affiliation: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Naumenko
authors.affiliation: Department of Pharmacology, Kuban' State Medical University, Sedina street, 4, Krasnodar, Russia.
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Galenko-Yaroshevsky
authors.affiliation: Department of Human and Animal Physiology, Biological Faculty of the Moscow State University, Leninskiye Gory, 1, 12, Moscow, Russia. abram340@mail.ru.|Department of Physiology, Pirogov Russian National Research Medical University, Ostrovityanova street, 1, Moscow, Russia. abram340@mail.ru.
authors.forename: Denis V
authors.initials: DV
authors.lastname: Abramochkin
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D021461:Animals, Outbred Strains; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000378:metabolism*; D002317:Cardiovascular Agents / Q000494:pharmacology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D055724:Electrophysiological Phenomena / Q000187:drug effects; D004928:Escin / Q000494:pharmacology; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D008839:Microelectrodes; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D043587:Receptor, Muscarinic M3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D020746:Calcium Channels, L-Type; D002317:Cardiovascular Agents; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D043587:Receptor, Muscarinic M3; D004928:Escin
keywords: Acetylcholine; Action potential; Atrium; Calcium current; Muscarinic receptors; Rat