Biomaterial Database

Inhibitory effect of amiodarone on the muscarinic acetylcholine receptor-operated potassium current in guinea pig atrial cells. 1996

Y Watanabe, and Y Hara, and M Tamagawa, and H Nakaya

Department of Pharmacology, Chiba University School of Medicine, Japan.

It is well known that amiodarone is effective for the treatment of atrial fibrillation. However, effects of amiodarone on the muscarinic acetylcholine receptor-operated K+ current (IK.ACh), which plays an important role in the repolarization of atrial action potential, have not been evaluated. This study was undertaken to determine whether amiodarone inhibits the acetyl-choline-sensitive muscarinic K+ (KACh) channel by use of the patch-clamp technique. In isolated guinea pig atrial cells, IK.ACh was activated by extracellular application of carbachol (1 microM) or adenosine (10 microM) or by the intracellular loading of GTP gamma S (100 microM). Amiodarone inhibited the IK.ACh activated in these three different ways with similar IC50 values around 2 microM, which indicated that amiodarone directly depresses the function of the KACh channel itself and/or GTP-binding proteins. Single KACh channel current was also recorded by use of a pipette solution containing carbachol (1 microM) or atropine (10 microM) plus theophylline (100 microM) in a cell-attached configuration. Amiodarone at a concentration of 3 microM significantly decreased the open probability of the KACh channel in both conditions. Amiodarone also reversed the carbachol- and adenosine-induced action potential shortening in a concentration-dependent manner. In isolated guinea pig hearts, perfusion of 1 microM carbachol shortened the effective refractory period of the atria and lowered the atrial fibrillation threshold. Addition of 10 microM amiodarone reversed these electrophysiological parameters to the control level. These results suggest that amiodarone inhibits IK.ACh by depressing the function of the KACh channel itself and/or associated GTP-binding proteins. This effect of amiodarone may at least in part be involved in the antiarrhythmic action against atrial fibrillation.

UI	MeSH Term	Description	Entries
D011976	Receptors, Muscarinic	One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.	Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine
D012032	Refractory Period, Electrophysiological	The period of time following the triggering of an ACTION POTENTIAL when the CELL MEMBRANE has changed to an unexcitable state and is gradually restored to the resting (excitable) state. During the absolute refractory period no other stimulus can trigger a response. This is followed by the relative refractory period during which the cell gradually becomes more excitable and the stronger impulse that is required to illicit a response gradually lessens to that required during the resting state.	Period, Neurologic Refractory,Periods, Neurologic Refractory,Refractory Period, Neurologic,Tetanic Fade,Vvedenskii Inhibition,Wedensky Inhibition,Inhibition, Vvedenskii,Inhibition, Wedensky,Neurologic Refractory Period,Neurologic Refractory Periods,Neuromuscular Fade,Neuromuscular Transmission Fade,Refractory Period, Neurological,Refractory Periods, Neurologic,Electrophysiological Refractory Period,Electrophysiological Refractory Periods,Fade, Neuromuscular,Fade, Neuromuscular Transmission,Fade, Tetanic,Neurological Refractory Period,Neurological Refractory Periods,Refractory Periods, Electrophysiological,Refractory Periods, Neurological,Transmission Fade, Neuromuscular
D002217	Carbachol	A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.	Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006321	Heart	The hollow, muscular organ that maintains the circulation of the blood.	Hearts
D000200	Action Potentials	Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.	Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000638	Amiodarone	An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.	Amiobeta,Amiodarex,Amiodarona,Amiodarone Hydrochloride,Amiohexal,Aratac,Braxan,Corbionax,Cordarex,Cordarone,Kordaron,L-3428,Ortacrone,Rytmarone,SKF 33134-A,Tachydaron,Trangorex,Hydrochloride, Amiodarone,L 3428,L3428,SKF 33134 A,SKF 33134A
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000889	Anti-Arrhythmia Agents	Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.	Anti-Arrhythmia Agent,Anti-Arrhythmia Drug,Anti-Arrhythmic,Antiarrhythmia Agent,Antiarrhythmia Drug,Antiarrhythmic Drug,Antifibrillatory Agent,Antifibrillatory Agents,Cardiac Depressant,Cardiac Depressants,Myocardial Depressant,Myocardial Depressants,Anti-Arrhythmia Drugs,Anti-Arrhythmics,Antiarrhythmia Agents,Antiarrhythmia Drugs,Antiarrhythmic Drugs,Agent, Anti-Arrhythmia,Agent, Antiarrhythmia,Agent, Antifibrillatory,Agents, Anti-Arrhythmia,Agents, Antiarrhythmia,Agents, Antifibrillatory,Anti Arrhythmia Agent,Anti Arrhythmia Agents,Anti Arrhythmia Drug,Anti Arrhythmia Drugs,Anti Arrhythmic,Anti Arrhythmics,Depressant, Cardiac,Depressant, Myocardial,Depressants, Cardiac,Depressants, Myocardial,Drug, Anti-Arrhythmia,Drug, Antiarrhythmia,Drug, Antiarrhythmic,Drugs, Anti-Arrhythmia,Drugs, Antiarrhythmia,Drugs, Antiarrhythmic
D001281	Atrial Fibrillation	Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.	Auricular Fibrillation,Familial Atrial Fibrillation,Paroxysmal Atrial Fibrillation,Persistent Atrial Fibrillation,Atrial Fibrillation, Familial,Atrial Fibrillation, Paroxysmal,Atrial Fibrillation, Persistent,Atrial Fibrillations,Atrial Fibrillations, Familial,Atrial Fibrillations, Paroxysmal,Atrial Fibrillations, Persistent,Auricular Fibrillations,Familial Atrial Fibrillations,Fibrillation, Atrial,Fibrillation, Auricular,Fibrillation, Familial Atrial,Fibrillation, Paroxysmal Atrial,Fibrillation, Persistent Atrial,Fibrillations, Atrial,Fibrillations, Auricular,Fibrillations, Familial Atrial,Fibrillations, Paroxysmal Atrial,Fibrillations, Persistent Atrial,Paroxysmal Atrial Fibrillations,Persistent Atrial Fibrillations