I(Kr) contributes to the altered ventricular repolarization that determines long-term cardiac memory

Area of Science:

• Cardiovascular Physiology
• Electrophysiology
• Molecular Cardiology

Background:

• Cardiac memory (CM) is defined by altered T-wave morphology, indicating changes in ventricular repolarization gradients.
• The specific ionic mechanisms underlying these repolarization changes in CM remain incompletely understood.

Purpose of the Study:

• To investigate the potential contribution of the delayed rectifier potassium currents, I(Kr) and I(Ks), to the altered repolarization observed in cardiac memory.
• To elucidate the role of transmural gradients in I(Kr) and I(Ks) in the development of cardiac memory.

Main Methods:

• Conscious dogs were subjected to ventricular pacing for three weeks to induce cardiac memory.
• Electrocardiograms (ECGs) were recorded throughout the pacing period.
• Post-pacing, hearts were excised for detailed electrophysiological and molecular analysis of epicardial and endocardial tissues and myocytes.

Main Results:

• Cardiac memory altered the transmural gradient of action potential duration (APD), diminishing the difference between epicardial and endocardial APD.
• A transmural gradient of I(Kr) (epicardium > endocardium) in controls was reversed in cardiac memory.
• Cardiac memory also altered the transmural gradient of I(Ks) and reduced epicardial expression of canine ERG (cERG) mRNA and protein.

Conclusions:

• A transcriptionally induced alteration in epicardial I(Kr) is a key contributor to the modified ventricular repolarization characteristic of cardiac memory.
• These findings highlight the role of specific ion channel changes in the electrophysiological remodeling associated with cardiac memory.