Remodeling of early-phase repolarization: a mechanism of abnormal impulse conduction in heart failure.

Circulation
Yanggan WangJoseph A Hill

Abstract

The early phase of action potential (AP) repolarization is critical to impulse conduction in the heart because it provides current for charging electrically coupled cells. In the present study we tested the impact of heart failure-associated electrical remodeling on AP propagation. Subepicardial, midmyocardial, and subendocardial myocytes were enzymatically dissociated from control and pressure-overload failing left ventricle (LV), and APs were recorded. A unique coupling-clamp technique was used to electrically couple 2 isolated myocytes with a controlled value of coupling conductance (Gc). In sham-operated mice, AP duration manifested a clear transmural gradient, with faster repolarization in subepicardial myocytes than in subendocardial myocytes. AP propagation from subendocardial to subepicardial myocytes required less Gc compared with conduction in the opposite direction. In failing heart, AP morphology was dramatically altered, with a significantly elevated plateau potential and prolonged AP duration. Spatially nonuniform alteration of AP duration in failing heart blunted the transmural gradient of repolarization. Furthermore, increased pacing rate prolonged AP duration exclusively in myocytes from failing heart, and the ...Continue Reading

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Citations

Nov 30, 2007·Acta Physiologica·M J KilleenC L-H Huang
Mar 17, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Yanggan WangBrian H Crawford
Jan 31, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Jun ChengYanggan Wang
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Nov 24, 2011·Journal of Molecular and Cellular Cardiology·Xiang LuoJoseph A Hill
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Aug 29, 2021·Cellular Signalling·Malay Chaklader, Beverly A Rothermel

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