Transmural action potential and ionic current remodeling in ventricles of failing canine hearts.
Heart failure (HF) produces important alterations in currents underlying cardiac repolarization, but the transmural distribution of such changes is unknown. We therefore recorded action potentials and ionic currents in cells isolated from the endocardium, midmyocardium, and epicardium of the left ventricle from dogs with and without tachypacing-induced HF. HF greatly increased action potential duration (APD) but attenuated APD heterogeneity in the three regions. Early afterdepolarizations (EADs) were observed in all cell types of failing hearts but not in controls. Inward rectifier K(+) current (I(K1)) was homogeneously reduced by approximately 41% (at -60 mV) in the three cell types. Transient outward K(+) current (I(to1)) was decreased by 43-45% at +30 mV, and the slow component of the delayed rectifier K(+) current (I(Ks)) was significantly downregulated by 57%, 49%, and 58%, respectively, in epicardial, midmyocardial, and endocardial cells, whereas the rapid component of the delayed rectifier K(+) current was not altered. The results indicate that HF remodels electrophysiology in all layers of the left ventricle, and the downregulation of I(K1), I(to1), and I(Ks) increases APD and favors occurrence of EADs.
Institute of Cardiovascular Science and Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China.
Gui-Rong
GR
Li
Chu-Pak
CP
Lau
Anique
A
Ducharme
Jean-Claude
JC
Tardif
Stanley
S
Nattel
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology; D004285:Dogs; D004699:Endocardium / Q000503:physiopathology; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D008297:Male; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology*
D020746:Calcium Channels, L-Type; D024661:Potassium Channels, Inwardly Rectifying; D011188:Potassium; D002118:Calcium