title: GIRK channel activation via adenosine or muscarinic receptors has similar effects on rat atrial electrophysiology.
abstract: G protein-coupled inwardly rectifying K⁺ channels (GIRK) are important in the regulation of heart rate and atrial electrophysiology. GIRK channels are activated by G protein-coupled receptors, including muscarinic M₂ receptors and adenosine A₁ receptors. The aim of this study was to characterize and compare the electrophysiological effects of acetylcholine (ACh) and adenosine on GIRK channels in rat atria. Action potential duration at 90% repolarization (APD₉₀), effective refractory period (ERP), and resting membrane potential (RMP) were investigated in isolated rat atria by intracellular recordings. Both the adenosine analog N6-cyclopentyladenosine (CPA) and ACh profoundly shortened APD₉₀ and ERP and hyperpolarized the RMP. No additive or synergistic effect of CPA and ACh coapplication was observed. To antagonize GIRK channel activation, the specific inhibitor rTertiapin Q (TTQ) was applied. The coapplication of TTQ reversed the CPA and ACh-induced effects. When TTQ was applied without exogenous receptor activator, both APD₉₀ and ERP were prolonged and RMP was depolarized, confirming a basal activity of the GIRK current. The results reveal that activation of A₁ and M₂ receptors has a profound and equal effect on the electrophysiology in rat atrium. This effect is to a major extent mediated through GIRK channels. Furthermore, these results support the notion that atrial GIRK currents from healthy hearts have a basal component and additional activation can be mediated via at least 2 different receptor mechanisms.
authors.affiliation: Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Liang
authors.forename: Lasse
authors.initials: L
authors.lastname: Skibsbye
authors.forename: Søren-Peter
authors.initials: SP
authors.lastname: Olesen
authors.forename: Morten
authors.initials: M
authors.lastname: Grunnet
authors.forename: Thomas
authors.initials: T
authors.lastname: Jespersen
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D016275:Atrial Function / Q000187:drug effects; D055724:Electrophysiological Phenomena / Q000187:drug effects; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2 / Q000819:agonists / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D049990:Membrane Transport Modulators; D026902:Potassium Channel Blockers; D058906:Purinergic P1 Receptor Agonists; D043585:Receptor, Muscarinic M2; D018340:Receptors, Adrenergic, alpha-1; D000241:Adenosine; D000109:Acetylcholine