Adenoviral Expression of I Ks Contributes to Wavebreak and Fibrillatory Conduction in Neonatal Rat Ventricular Cardiomyocyte Monolayers
Autor: | José Jalife, Sandeep V. Pandit, Viviana Muñoz, Sergey Mironov, Steven M. Taffet, Krzysztof R. Grzeda, André G. Kléber, Thomas Desplantez, Stephan Rohr |
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Rok vydání: | 2007 |
Předmět: |
medicine.medical_specialty
DNA Complementary Physiology Refractory period Heart Ventricles Action Potentials Adenoviridae Rats Sprague-Dawley Heart Conduction System Internal medicine Optical mapping Receptors Adrenergic beta medicine Animals Ventricular Function Myocytes Cardiac KvLQT1 Cells Cultured Fibrillatory conduction Neonatal rat biology Arrhythmias Cardiac Reentry Rats Electrophysiology Endocrinology Animals Newborn Potassium Channels Voltage-Gated KCNQ1 Potassium Channel Circulatory system biology.protein Cardiology Action potential duration Cardiology and Cardiovascular Medicine |
Zdroj: | Circulation Research. 101:475-483 |
ISSN: | 1524-4571 0009-7330 |
DOI: | 10.1161/circresaha.107.149617 |
Popis: | Previous studies have shown that the gating kinetics of the slow component of the delayed rectifier K + current ( I Ks ) contribute to postrepolarization refractoriness in isolated cardiomyocytes. However, the impact of such kinetics on arrhythmogenesis remains unknown. We surmised that expression of I Ks in rat cardiomyocyte monolayers contributes to wavebreak formation and facilitates fibrillatory conduction by promoting postrepolarization refractoriness. Optical mapping was performed in 44 rat ventricular myocyte monolayers infected with an adenovirus carrying the genomic sequences of KvLQT1 and minK (molecular correlates of I Ks ) and 41 littermate controls infected with a GFP adenovirus. Repetitive bipolar stimulation was applied at increasing frequencies, starting at 1 Hz until loss of 1:1 capture or initiation of reentry. Action potential duration (APD) was significantly shorter in I Ks -infected monolayers than in controls at 1 to 3 Hz ( P I Ks group. Wavelengths in the latter were significantly shorter than in controls at all rotation frequencies. Wavebreaks leading to fibrillatory conduction occurred in 45% of the I Ks reentry episodes but in none of the controls. Moreover, the density of wavebreaks increased with time as long as a stable source sustained the fibrillatory activity. These results provide the first demonstration that I Ks -mediated postrepolarization refractoriness can promote wavebreak formation and fibrillatory conduction during pacing and sustained reentry and may have important implications in tachyarrhythmias. |
Databáze: | OpenAIRE |
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