title: G-protein-coupled inward rectifier potassium current contributes to ventricular repolarization.
abstract: OBJECTIVE
  The purpose of this study was to investigate the functional role of G-protein-coupled inward rectifier potassium (GIRK) channels in the cardiac ventricle.
  
  
  RESULTS
  Immunofluorescence experiments demonstrated that GIRK4 was localized in outer sarcolemmas and t-tubules in GIRK1 knockout (KO) mice, whereas GIRK4 labelling was not detected in GIRK4 KO mice. GIRK4 was localized in intercalated discs in rat ventricle, whereas it was expressed in intercalated discs and outer sarcolemmas in rat atrium. GIRK4 was localized in t-tubules and intercalated discs in human ventricular endocardium and epicardium, but absent in mid-myocardium. Electrophysiological recordings in rat ventricular tissue ex vivo showed that the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and acetylcholine (ACh) shortened action potential duration (APD), and that the APD shortening was reversed by either the GIRK channel blocker tertiapin-Q, the adenosine A1 receptor antagonist DPCPX or by the muscarinic M2 receptor antagonist AF-DX 116. Tertiapin-Q prolonged APD in the absence of the exogenous receptor activation. Furthermore, CPA and ACh decreased the effective refractory period and the effect was reversed by either tertiapin-Q, DPCPX or AF-DX 116. Receptor activation also hyperpolarized the resting membrane potential, an effect that was reversed by tertiapin-Q. In contrast, tertiapin-Q depolarized the resting membrane potential in the absence of the exogenous receptor activation.
  
  
  CONCLUSIONS
  Confocal microscopy shows that among species GIRK4 is differentially localized in the cardiac ventricle, and that it is heterogeneously expressed across human ventricular wall. Electrophysiological recordings reveal that GIRK current may contribute significantly to ventricular repolarization and thereby to cardiac electrical stability.
authors.affiliation: Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 16.5.35, Copenhagen DK-2200N, Denmark.
authors.forename: Bo
authors.initials: B
authors.lastname: Liang
authors.forename: Jakob D
authors.initials: JD
authors.lastname: Nissen
authors.forename: Morten
authors.initials: M
authors.lastname: Laursen
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.forename: Lasse
authors.initials: L
authors.lastname: Skibsbye
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Hearing
authors.forename: Martin N
authors.initials: MN
authors.lastname: Andersen
authors.forename: Hanne B
authors.initials: HB
authors.lastname: Rasmussen
authors.forename: Kevin
authors.initials: K
authors.lastname: Wickman
authors.forename: Morten
authors.initials: M
authors.lastname: Grunnet
authors.forename: Søren-Peter
authors.initials: SP
authors.lastname: Olesen
authors.forename: Thomas
authors.initials: T
authors.lastname: Jespersen
mesh_terms: D000818:Animals; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism*; D006801:Humans; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D011188:Potassium / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; C484273:Kcnj5 protein, mouse; D011188:Potassium
keywords: Acetylcholine; Action potential; Adenosine; GIRK channel; Repolarization