Decreased inward rectifying K+ current and increased ryanodine receptor sensitivity synergistically contribute to sustained focal arrhythmia in the intact rabbit heart.

The Journal of Physiology
Rachel C MylesCrystal M Ripplinger

Abstract

Heart failure leads to dramatic electrophysiological remodelling as a result of numerous cellular and tissue-level changes. Important cellular changes include increased sensitivity of ryanodine receptors (RyRs) to Ca(2+) release and down-regulation of the inward rectifying K(+) current (IK1), both of which contribute to triggered action potentials in isolated cells. We studied the role of increased RyR sensitivity and decreased IK1 in contributing to focal arrhythmia in the intact non-failing rabbit heart using optical mapping and pharmacological manipulation of RyRs and IK1. Neither increased RyR sensitivity or decreased IK1 alone led to significant increases in arrhythmia following local sympathetic stimulation; however, in combination, these two factors led to a significant increase in premature ventricular complexes and focal ventricular tachycardia. These results suggest synergism between increased RyR sensitivity and decreased IK1 in contributing to focal arrhythmia in the intact heart and may provide important insights into novel anti-arrhythmic treatments in heart failure. Heart failure (HF) results in dramatic electrophysiological remodelling, including increased sensitivity of ryanodine receptors (RyRs) and decreased ...Continue Reading

References

Dec 1, 1986·Biophysical Journal·R W Joyner, F J van Capelle
Jan 3, 2001·Journal of Applied Physiology·M P NashD J Paterson
Feb 13, 2001·Journal of Molecular and Cellular Cardiology·E DupontN J Severs
Nov 8, 2001·American Journal of Physiology. Cell Physiology·J L Puglisi, D M Bers
Jan 17, 2002·The New England Journal of Medicine·H V HuikuriR J Myerburg
Feb 26, 2003·Circulation Research·Kenneth R LauritaMichael H Koo
Jan 17, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Wei LiBeth A Habecker
Oct 16, 2004·Circulation Research·Gordon F Tomaselli, Douglas P Zipes
Feb 12, 2005·American Journal of Physiology. Heart and Circulatory Physiology·David O ArnarJames B Martins
Jun 1, 2005·Lancet·John J V McMurray, Marc A Pfeffer
May 1, 2007·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Vadim V FedorovIgor R Efimov
Nov 17, 2007·Cardiovascular Research·Luigi A VenetucciDavid A Eisner
May 16, 2008·Journal of Cardiovascular Electrophysiology·Harish DoppalapudiJian Huang
Feb 17, 2009·The Journal of Physiology·Gordon B Drummond
Jul 14, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Lin WuLuiz Belardinelli
Aug 4, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Gregory S HoekerKenneth R Laurita
Apr 28, 2012·Circulation Research·Rachel C MylesCrystal M Ripplinger

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Citations

Mar 17, 2015·The Journal of Physiology·Donald M Bers, Ye Chen-Izu
Jan 19, 2016·Progress in Biophysics and Molecular Biology·Crystal M RipplingerDominik Linz
Jun 5, 2016·Cardiac Electrophysiology Clinics·Lasse Skibsbye, Ursula Ravens
Apr 21, 2016·Journal of Pharmacological and Toxicological Methods·Emily R PfeifferRoss Whittaker
Apr 10, 2016·The Journal of Physiology·Beth A HabeckerCrystal M Ripplinger
Oct 24, 2015·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Thomas H FischerSamuel Sossalla
Oct 25, 2016·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Donald M Bers
Jan 27, 2016·Circulation. Arrhythmia and Electrophysiology·Ryan T GardnerBeth A Habecker
Jun 6, 2015·Circulation Research·Stefan WagnerDonald M Bers
Oct 31, 2018·Frontiers in Physiology·Daniel M Johnson, Gudrun Antoons
Mar 27, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Rafael JaimesMatthew W Kay
Apr 12, 2017·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Michael G KleinMark C Haigney
Apr 16, 2021·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Louise Reilly, Lee L Eckhardt

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