TITLE

G-protein-coupled inward rectifier potassium current contributes to ventricular repolarization

AUTHOR(S)
Liang, Bo; Nissen, Jakob D.; Laursen, Morten; Wang, Xiaodong; Skibsbye, Lasse; Hearing, Matthew C.; Andersen, Martin N.; Rasmussen, Hanne B.; Wickman, Kevin; Grunnet, Morten; Olesen, Søren-Peter; Jespersen, Thomas
PUB. DATE
January 2014
SOURCE
Cardiovascular Research;Jan2014, Vol. 101 Issue 1, p175
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Aims The purpose of this study was to investigate the functional role of G-protein-coupled inward rectifier potassium (GIRK) channels in the cardiac ventricle. Methods and 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. Conclusion 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.
ACCESSION #
93398945

 

Related Articles

  • Differential expression of the melanocortin-4 receptor in male and female C57BL/6J mice. Qu, HaiE; Li, JianPing; Chen, Wei; Li, YuMei; Jiang, Qian; Jiang, HuaiZhi; Huo, JinLong; Zhao, ZhiHui; Liu, Bo; Zhang, QiaoLing // Molecular Biology Reports;May2014, Vol. 41 Issue 5, p3245 

    The melanocortin 4 receptor is a member of melanocortin receptors of G-protein-coupled receptors. By binding to melanocortin receptor agonists or antagonists, MC4R participates in the regulating of food intake, weight, energy homeostasis and sexual behavior. By activating the protein kinase A...

  • The agonist-specific voltage dependence of M2 muscarinic receptors modulates the deactivation of the acetylcholine-gated K current ( I). Moreno-Galindo, Eloy; Alamilla, Javier; Sanchez-Chapula, José; Tristani-Firouzi, Martin; Navarro-Polanco, Ricardo // Pflugers Archiv European Journal of Physiology;Jul2016, Vol. 468 Issue 7, p1207 

    Recently, it has been shown that G protein-coupled receptors (GPCRs) display intrinsic voltage sensitivity. We reported that the voltage sensitivity of M2 muscarinic receptor (M2R) is also ligand specific. Here, we provide additional evidence to understand the mechanism underlying the...

  • Electrophysiological characteristics of heart ventricular papillary muscles in diabetic histidine decarboxylase knockout and wild-type mice. András Falus; Valéria Kecskeméti // Journal of Interventional Cardiac Electrophysiology;Dec2009, Vol. 26 Issue 3, p155 

    Abstract Objective  The diabetes-induced action potential (AP) abnormalities have been studied mainly in rats where significant prolongation of repolarization and reduced maximum rate of depolarization (V max) was detected. Histidine decarboxylase knockout (HDC-KO) mice lack...

  • Effect of Selective Stimulation of Muscarinic M Cholinoceptors on Electrical and Contractile Activity of Rat Ventricular Myocardium. Abramochkin, D.; Tapilina, S.; Sukhova, G. // Bulletin of Experimental Biology & Medicine;Jan2013, Vol. 154 Issue 3, p295 

    We studied the effect of selective activation of muscarinic M receptors on electrical activity in the isolated preparation of rat ventricular myocardium as well as contractile activity of the left ventricle of Langendorff-perfused isolated heart. Application of muscarinic agonist pilocarpine (10...

  • Gαi2- and Gαi3-Deficient Mice Display Opposite Severity of Myocardial Ischemia Reperfusion Injury. Köhler, David; Devanathan, Vasudharani; Bernardo de Oliveira Franz, Claudia; Eldh, Therese; Novakovic, Ana; Roth, Judith M.; Granja, Tiago; Birnbaumer, Lutz; Rosenberger, Peter; Beer-Hammer, Sandra; Nürnberg, Bernd // PLoS ONE;May2014, Vol. 9 Issue 5, p1 

    G-protein-coupled receptors (GPCRs) are the most abundant receptors in the heart and therefore are common targets for cardiovascular therapeutics. The activated GPCRs transduce their signals via heterotrimeric G-proteins. The four major families of G-proteins identified so far are specified...

  • Proarrhythmia in a non-failing murine model of cardiac-specific Na/Ca exchanger overexpression: whole heart and cellular mechanisms. Pott, Christian; Muszynski, Adam; Ruhe, Matthias; Bögeholz, N.; Schulte, Jan; Milberg, Peter; Mönnig, Gerold; Fabritz, Larissa; Goldhaber, Joshua; Breithardt, Günter; Schmitz, Wilhelm; Philipson, Kenneth; Eckardt, Lars; Kirchhof, Paulus; Müller, Frank // Basic Research in Cardiology;Mar2012, Vol. 107 Issue 2, p1 

    The cardiac Na/Ca exchanger (NCX) generates an inward electrical current during SR-Ca release, thus possibly promoting afterdepolarizations of the action potential (AP). We used transgenic mice 12.5 weeks or younger with cardiomyocyte-directed overexpression of NCX (NCX-Tg) to study the...

  • Caveolin-1 limits the contribution of BK(Ca) channel to EDHF-mediated arteriolar dilation: implications in diet-induced obesity. Feher, Attila; Rutkai, Ibolya; Beleznai, Timea; Ungvari, Zoltan; Csiszar, Anna; Edes, Istvan; Bagi, Zsolt // Cardiovascular Research;Sep2010, Vol. 87 Issue 4, p732 

    Aims Caveolin-1 (Cav-1) interacts with large conductance Ca2+-activated potassium channels (BKCa) and likely exerts a negative regulatory effect on the channel activity. We investigated the role of Cav-1 in modulating BK(Ca) channel-mediated, endothelium-derived hyperpolarizing factor...

  • Synaptic physiology: No return for spiking axons. Lewis, Sian // Nature Reviews Neuroscience;Aug2012, Vol. 13 Issue 8, p517 

    The article focuses on the research study which show ectopic action potentials in distal axons of CA3 pyramidal cells produced in mouse hippocampal slices that were induced with gamma oscillations.

  • New mechanism for glutamate hypothesis in epilepsy. Chang-Hoon Cho // Frontiers in Cellular Neuroscience;Aug2013, Vol. 7, p1 

    The author discusses the study which examines two proposed hypotheses for mechanism in epilepsy. He cites that the study provides a new way of thinking that TREK-1, a two-pore potassium channel, can be responsible for fast glutamate release and Bestrophin-1 (Best1), a calcium activated anion...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics