Muscarinic agonists inhibit the ATP-dependent potassium current and suppress the ventricle-Purkinje action potential dispersion

Activation of the parasympathetic nervous system has been reported to have an antiarrhythmic role during ischemia-reperfusion injury by decreasing the arrhythmia triggers. Furthermore, it was reported that the parasympathetic neurotransmitter acetylcholine is able to modulate the ATP-dependent K-cur...

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Main Authors: Magyar Tibor
Árpádffy-Lovas Tamás
Pászti Bence József
Tóth Noémi
Szlovák Jozefina
Gazdag Péter
Kohajda Zsófia
Gurabi Zsolt
Jost Norbert László
Virág László
Papp Gyula
Nagy Norbert
Koncz Istvan
Format: Article
Published: 2021
Series:CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 99 No. 2
doi:10.1139/cjpp-2020-0408

mtmt:31709067
Online Access:http://publicatio.bibl.u-szeged.hu/21621
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520 3 |a Activation of the parasympathetic nervous system has been reported to have an antiarrhythmic role during ischemia-reperfusion injury by decreasing the arrhythmia triggers. Furthermore, it was reported that the parasympathetic neurotransmitter acetylcholine is able to modulate the ATP-dependent K-current (IK-ATP), a crucial current activated during hypoxia. However, the possible significance of this current modulation in the antiarrhythmic mechanism is not fully clarified.Action potentials were measured using the conventional microelectrode technique from canine left ventricular papillary muscle and free-running Purkinje fibers, under normal and hypoxic conditions. Ionic currents were measured using the whole-cell configuration of the patch clamp method.5 μM acetylcholine did not influence the action potential duration (APD) either in Purkinje fibers or in papillary muscle preparations. In contrast, it significantly lengthened the APD and suppressed the Purkinje-ventricle APD dispersion when it was administered after 5 μM pinacidil application. 3 μM carbachol reduced the pinacidil-activated IK-ATP under voltage-clamp condition. Acetylcholine lengthened the ventricular action potential under simulated ischemia condition.In this study we found that acetylcholine inhibits the IK-ATP and thus suppresses the ventricle-Purkinje APD dispersion. We conclude that parasympathetic tone may reduce the arrhythmogenic substrate exerting a complex antiarrhythmic mechanism during hypoxic conditions. 
700 0 2 |a Árpádffy-Lovas Tamás  |e aut 
700 0 2 |a Pászti Bence József  |e aut 
700 0 2 |a Tóth Noémi  |e aut 
700 0 2 |a Szlovák Jozefina  |e aut 
700 0 2 |a Gazdag Péter  |e aut 
700 0 2 |a Kohajda Zsófia  |e aut 
700 0 2 |a Gurabi Zsolt  |e aut 
700 0 2 |a Jost Norbert László  |e aut 
700 0 2 |a Virág László  |e aut 
700 0 2 |a Papp Gyula  |e aut 
700 0 2 |a Nagy Norbert  |e aut 
700 0 2 |a Koncz Istvan  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/21621/1/2020-Magyaretal.pdf  |z Dokumentum-elérés