Excitatory effect of M1 muscarinic acetylcholine receptor on automaticity of mouse heart.
We have investigated the effects of relatively high concentration of carbachol (CCh), an agonist of muscarinic acetylcholine receptor (mAChR), on cardiac automaticity in mouse heart. Action potentials from automatically beating right atria of mice were measured with conventional microelectrodes. When atria were treated with 100 microM CCh, atrial beating was immediately arrested and diastolic membrane potential (DMP) was depolarized. After exposure of the atria to CCh for approximately 4 min, action potentials were regenerated. The regenerated action potentials had lower frequency and shorter duration when compared with the control. When atria were pre-exposed to pirenzepine (1 microM), an M1 mAChR antagonist, there was complete inhibition of CCh-induced depolarization of DMP and regeneration of action potentials. Pre-exposure to AFDX-116 (11 ({2-[(diethylamino)-methyl]-1 -piperidyl}acetyl)-5,11 -dihydro-6H-pyridol[2,3-b][1,4] benzodiazepine-6-one base, 1 microM), an M2 mAChR antagonist, failed to block CCh-induced arrest of the beating. However, prolonged exposure to CCh elicited gradual depolarization of DMP and slight acceleration in beating rate. Our data indicate that high concentration of CCh depolarizes membrane potential and recovers right atrial automaticity via M1 mAChR, providing functional evidence for the role of M1 mAChR in the atrial myocytes.
Woo
Sun-Hee
SH
College of Pharmacy, Chungnam National University, 220 Gung-Dong, Yuseong-Ku, Daejeon 305-764, Korea. shwoo@cnu.ac.kr
Lee
Byung Ho
BH
Kwon
Kwang-Il
KI
Lee
Chin Ok
CO
D000200:Action Potentials; D000818:Animals; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D043643:Receptor, Muscarinic M1 / Q000819:agonists* / Q000378:metabolism; D013268:Stimulation, Chemical
D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D010890:Pirenzepine; D002217:Carbachol