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Updated: May 7, 2026
08:34
Isolation of Atrial Myocytes from Adult Mice
Published on: July 25, 2019
Atrium-specific Kir3.x determines inducibility, dynamics, and termination of fibrillation by regulating
Brian O Bingen1, Zeinab Neshati, Saïd F A Askar
1Laboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands (B.O.B., Z.N., S.F.A.A., D.L.Y., M.J.S., A.A.V.d.V., D.A.P.); and Department of Physics and Astronomy, Ghent University, Ghent, Belgium (I.V.K., A.V.P.).
Circulation
|September 26, 2013
Summary
Blocking atrium-specific Kir3.x channels effectively terminates atrial fibrillation by prolonging action potential duration. This study identifies Kir3.x as a promising target for new antiarrhythmic drugs.
Area of Science:
- Cardiology
- Molecular Biology
- Electrophysiology
Background:
- Atrial fibrillation is a common arrhythmia.
- Ventricular proarrhythmia complicates treatment.
- Atrium-specific Kir3.x channels generate a constitutively active current (I(K,ACh-c)) after atrial remodeling.
Purpose of the Study:
- Investigate the role of I(K,ACh-c) in atrial fibrillation induction, dynamics, and termination.
- Evaluate the effects of I(K,ACh-c) blockade and Kir3.x downregulation on atrial fibrillation.
Main Methods:
- Used neonatal rat atrial cardiomyocyte cultures and intact atria.
- Induced reentry through burst pacing.
- Treated cultures with tertiapin or used lentiviral vectors for Kcnj3/Kcnj5 shRNA.
- Performed whole-heart mapping experiments.
Main Results:
- Tertiapin prolonged action potential duration (APD) in atrial cultures during reentry.
- I(K,ACh-c) blockade decreased rotor frequency and complexity.
- Knockdown of Kcnj3 or Kcnj5 yielded similar results.
- Blockade prevented/terminated reentry by altering APD and conduction velocity restitution slopes.
- Reduced atrial fibrillation inducibility by over 50% after I(K,ACh-c) blockade.
Conclusions:
- Atrium-specific Kir3.x channels control atrial fibrillation induction, dynamics, and termination.
- Modulation of APD and restitution slopes by I(K,ACh-c) is key.
- Kir3.x is a promising atrium-specific target for antiarrhythmic strategies.
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