Adenoviral expression of IKs contributes to wavebreak and fibrillatory conduction in neonatal rat ventricular cardiomyocyte monolayers

Muñoz, Viviana; Grzeda, Krzysztof R; Desplantez, Thomas; Pandit, Sandeep V; Mironov, Sergey; Taffet, Steven M; Rohr, Stephan; Kléber, André G; Jalife, José (2007). Adenoviral expression of IKs contributes to wavebreak and fibrillatory conduction in neonatal rat ventricular cardiomyocyte monolayers. Circulation research, 101(5), pp. 475-83. Baltimore, Md.: Lippincott Williams & Wilkins 10.1161/CIRCRESAHA.107.149617

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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<0.05), whereas differences at higher pacing frequencies did not reach statistical significance. Stable rotors occurred in both groups, with significantly higher rotation frequencies, lower conduction velocities, and shorter action potentials in the 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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology
UniBE Contributor:	Rohr, Stephan
ISSN:	0009-7330
ISBN:	17626898
Publisher:	Lippincott Williams & Wilkins
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:53
Last Modified:	05 Dec 2022 14:16
Publisher DOI:	10.1161/CIRCRESAHA.107.149617
PubMed ID:	17626898
Web of Science ID:	000249155000008
URI:	https://boris.unibe.ch/id/eprint/22298 (FactScience: 33918)