Repolarization Reserve and Action Potential Dynamics in Failing Myocytes
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See Article by Hegyi et al
Prolongation of action potential duration (APD) is typically observed in isolated myocytes from both humans and animals with heart failure (HF) and is generally thought to be an important arrhythmia substrate. Traditionally, voltage-clamp studies have found that in addition to increased Na+/Ca2+ exchange and late Na+ currents, repolarizing currents, including the inward rectifier K+ (IK1) and delayed rectifier K+ (IKs, IKr) currents, are decreased in HF.1,2 These changes are expected to significantly prolong repolarization; however, this is not often observed at faster beating rates in failing myocytes3 and HF patients.4 In this issue of the Journal, Hegyi et al5 contend that more physiological conditions are required to understand the mechanisms of repolarization dynamics in HF myocytes. To this end, they used an elegant action potential (AP)–clamp technique to unravel the role and regulation of K+ currents6 under more realistic physiological conditions.
Hegyi et al5 report that when more realistic physiological conditions are used by leaving Ca2+ cycling intact, APD in failing isolated myocytes is prolonged at slow beating rates but similar to control myocytes at faster, near normal rates. In contrast, APD prolongation was observed in HF versus control at all beating rates studied when 10 mmol/L 1,2-bis(o-aminophenoxy)ethane-N,N,N‘,N‘-tetraacetic acid (BAPTA) was applied to prevent [Ca2+]i transients. The lack of significant APD prolongation at faster rates with Ca2+ cycling left intact is consistent with ECG QTc …