Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation.

The Journal of Physiology
Ning LiNipavan Chiamvimonvat

Abstract

Small conductance Ca(2+)-activated K(+) channels (SK channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca(2+) (Ca(2+)(i)) with membrane potential. We have recently reported the functional existence of SK2 channels in human and mouse cardiac myocytes. Moreover, we have found that the channel is predominantly expressed in atria compared to the ventricular myocytes. We hypothesize that knockout of SK2 channels may be sufficient to disrupt the intricate balance of the inward and outward currents during repolarization in atrial myocytes. We further predict that knockout of SK2 channels may predispose the atria to tachy-arrhythmias due to the fact that the late phase of the cardiac action potential is highly susceptible to aberrant excitation. We take advantage of a mouse model with genetic knockout of the SK2 channel gene. In vivo and in vitro electrophysiological studies were performed to probe the functional roles of SK2 channels in the heart. Whole-cell patch-clamp techniques show a significant prolongation of the action potential duration prominently in late cardiac repolarization in atrial myocytes from the heterozygous and homozygous null mutant animals. Moreover, in vivo e...Continue Reading

References

Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Nov 15, 1996·Circulation·C I BerulM E Mendelsohn
Mar 27, 1997·The New England Journal of Medicine·R BrugadaR Roberts
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·T M IshiiJ Maylie
Aug 4, 1998·Current Opinion in Neurobiology·C VergaraJ P Adelman
Jul 17, 1999·The American Journal of Physiology·H B NussE Marbán
Jul 22, 1999·Annals of the New York Academy of Sciences·C T BondJ P Adelman
Jul 27, 1999·Current Opinion in Chemical Biology·G J Kaczorowski, M L Garcia
Feb 24, 2001·Journal of the American College of Cardiology·S S ChughB J Gersh
Mar 10, 2001·Cell·M T Keating, M C Sanguinetti
Jun 23, 2001·Journal of the American College of Cardiology·P KovoorD E Clapham
Dec 13, 2002·Nature·Gilberto R SambranoJames T Stull
Jan 11, 2003·Science·Yi-Han ChenWei Huang
Jun 5, 2003·Circulation·Patrick T EllinorCalum A MacRae
Sep 3, 2003·Journal of Cardiovascular Electrophysiology·Patrick T Ellinor, Calum A Macrae
Sep 19, 2003·The Journal of Biological Chemistry·Yanfang XuNipavan Chiamvimonvat
Nov 25, 2003·Cardiology·Ling-Ping LaiShoei K Stephen Huang
Dec 17, 2003·Circulation·Ramon BrugadaCharles Antzelevitch
Jun 11, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Chris T BondJohn P Adelman
Apr 15, 2005·Journal of Cardiovascular Electrophysiology·Kui HongRamon Brugada
May 10, 2005·Journal of Cardiovascular Electrophysiology·Ramon Brugada
Jun 1, 2005·Cardiovascular Research·Ans C P WiesfeldIsabelle C Van Gelder
Jun 1, 2005·Current Opinion in Neurobiology·Chris T BondJohn P Adelman
Aug 2, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Dipika TutejaNipavan Chiamvimonvat
Sep 27, 2005·Physiological Reviews·Jeanne M Nerbonne, Robert S Kass
Apr 29, 2006·Nature Clinical Practice. Cardiovascular Medicine·Robert Roberts
Jun 15, 2006·Human Molecular Genetics·Timothy M OlsonAndre Terzic
Nov 18, 2006·Circulation Research·Ling LuNipavan Chiamvimonvat
Nov 30, 2006·Proceedings of the National Academy of Sciences of the United States of America·Danyan XuNipavan Chiamvimonvat
Dec 22, 2007·Circulation Research·Qian ZhangNipavan Chiamvimonvat

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Citations

Jan 19, 2010·Naunyn-Schmiedeberg's Archives of Pharmacology·Ursula Ravens
May 17, 2013·Journal of Human Genetics·Jae-Jung KimUNKNOWN Korean Kawasaki Disease Genetics Consortium
Aug 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Gennady CherednichenkoIsaac N Pessah
Apr 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·David WeisbrodBernard Attali
Aug 18, 2012·Antioxidants & Redox Signaling·Nitin T Aggarwal, Jonathan C Makielski
Aug 17, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Valeriy TimofeyevNipavan Chiamvimonvat
Aug 2, 2011·The Journal of Clinical Investigation·Reza WakiliStanley Nattel
Oct 25, 2011·Circulation Journal : Official Journal of the Japanese Circulation Society·Shu-Hsuan ChangChia-Ti Tsai
Aug 8, 2013·PloS One·Isik TurkerTomohiko Ai
Dec 4, 2013·Cardiovascular Research·Saagar MahidaPatrick T Ellinor
Jan 5, 2014·Cardiovascular Research·Stanley Nattel, Xiao Yan Qi
May 16, 2014·Nature Communications·Alicia D'SouzaMark R Boyett
Apr 1, 2014·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Saagar Mahida
Feb 20, 2013·Circulation. Arrhythmia and Electrophysiology·Yu-Cheng HsiehPeng-Sheng Chen
Jan 5, 2016·Acta Pharmacologica Sinica·David WeisbrodBernard Attali
May 20, 2015·Circulation Journal : Official Journal of the Japanese Circulation Society·Hyewon ParkBoyoung Joung
Jun 22, 2014·Proceedings of the National Academy of Sciences of the United States of America·Sassan RafizadehNipavan Chiamvimonvat
Feb 27, 2016·Expert Opinion on Therapeutic Targets·Jules C HancoxDierk Thomas
Dec 3, 2016·The Journal of Physiology·Matthew KennedyDaisuke Sato
Oct 25, 2016·Pharmacology & Therapeutics·Ursula Ravens, Katja E Odening
Apr 7, 2018·PloS One·Brandon ChalazanDawood Darbar
Dec 8, 2017·Scientific Reports·Young-Woo NamMiao Zhang
Mar 26, 2013·Journal of the American Heart Association·Po-Cheng ChangTomohiko Ai
Jun 22, 2010·Circulation. Arrhythmia and Electrophysiology·Jonas Goldin DinessRie Schultz Hansen
Dec 20, 2014·Circulation. Arrhythmia and Electrophysiology·Amrish DeshmukhMina K Chung
Apr 26, 2014·Circulation Research·Nathan R Tucker, Patrick T Ellinor
Jul 22, 2016·Medicine·Chih-Chieh YuJiunn-Lee Lin

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