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Transient outward current, Ito1, is altered in cardiac memory.

H Yu¹, D McKinnon, J E Dixon

¹Departments of Physiology, State University of New York at Stony Brook, Stony Brook, NY, USA.

|April 13, 1999

Summary

Long-term cardiac memory (LTM) in dogs alters T-wave morphology and action potentials. Changes in the transient outward current (Ito) are linked to these LTM effects.

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Area of Science:

Cardiology
Electrophysiology
Molecular Biology

Background:

Cardiac memory is a phenomenon where altered T-wave morphology persists after abnormal heart rhythms.
Understanding the cellular mechanisms underlying cardiac memory is crucial for diagnosing and treating cardiac conditions.

Purpose of the Study:

To investigate the electrophysiological and molecular changes associated with long-term cardiac memory (LTM) in a canine model.
To determine the role of the transient outward potassium current (Ito) in LTM-induced cardiac alterations.

Main Methods:

Long-term cardiac memory (LTM) was induced in conscious dogs by ventricular pacing for 3 weeks.
Electrocardiograms (ECGs) and epicardial action potentials were recorded.
Whole-cell patch clamp techniques were used to study the transient outward current (Ito) in left ventricular epicardial myocytes.
Messenger RNA (mRNA) levels for Kv4.3 were assessed.

Main Results:

LTM induced significant changes in T-wave amplitude and vector on ECGs.
Epicardial action potentials showed a loss of notch and prolonged duration in LTM myocytes.
The transient outward current (Ito) activation showed a positive voltage shift, reduced density, and significantly prolonged recovery from inactivation in LTM myocytes.
Decreased Kv4.3 mRNA levels were observed in LTM myocytes.

Conclusions:

Alterations in the transient outward current (Ito) are closely associated with the observed action potential and T-wave changes in long-term cardiac memory.
These Ito changes provide a partial explanation for the electrophysiological manifestations of LTM.