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KMID : 0614020040190010078
Journal of Pharmaceutical Sciences (C.N.U.)
2004 Volume.19 No. 1 p.78 ~ p.81
Stimulatory Effect of Cabachol via M©û Muscarinic Receptor on Spontaneous Action Potential in Mouse Atrium
Woo Sun-Hee

Shin Hee-Sup
Lee Chin-Ok
Abstract
Muscarinic stimulation in the heart is known to reduce heart rate and excitability of cardiac cell membrane. In the present study we examined the effects of carbachol (CCh), a muscarinic acetylcholine receptor (mAChR) agonist, on action potentials spontaneously occurring from the right atrium, using conventional microelectrode technique Relatively high concentration of CCh (100 ¥ìM) immediately stopped the heartbeat, and induced transient hyperpolarization followed by depolarization of diastolic membrane potential. The CCh-induced late depolarization resumed spontaneous action potentials following 4-5 min of its onset although the rate of action potential was slower than the control. The rate and diastolic membrane potentials of rebound action potentials showed several oscillations in the beginning, which was then stabilized. In the presence of M©û mAChR antagonist, pirenzepine, CCh stopped the beat and hyperpolarized membrane potential, but it did not produce the depolarization and rebound action potentials. M©ü mAChR antagonist, AFDX-116, suppressed CCh-mediated arrest of beat, but not the depolarization. In the presence of AFDX-116 CCh slightly enhanced the rate of beat. Our data suggest that acetylcholine plays dual opposing roles, suppression via M©ü mAChR and stimulation via M©û mAChR, in the regulation of cardiac spontaneous action potential.
KEYWORD
muscarinic acetylcholine receptor, cabachol, spontaneous action potential, atrium
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