An altered repolarizing potassium current in rat cardiac myocytes after subtotal nephrectomy

Area of Science:

• Cardiology
• Nephrology
• Electrophysiology

Background:

• Renal failure is linked to electrocardiographic changes and poor cardiac prognosis.
• Abnormal cardiac myocyte repolarization is suggested by altered QT interval dispersion in renal failure patients.

Purpose of the Study:

• To investigate alterations in cardiac myocyte repolarizing currents in rats with renal failure.
• To determine the impact of subtotal nephrectomy (SNx) on specific potassium currents and action potential duration.

Main Methods:

• Whole-cell patch-clamp technique was used to measure repolarizing K(+) currents in isolated cardiac myocytes from SNx and control rats.
• Monophasic cardiac action potentials were recorded from isolated perfused hearts.
• 4-aminopyridine (4-AP)-sensitive transient outward (I(to)) and 4-AP-insensitive sustained outward (I(so)) currents were quantified.

Main Results:

• SNx rats exhibited cardiac hypertrophy and fibrosis but not hypertension.
• A two- to threefold increase and greater heterogeneity in I(to) were observed in SNx myocytes.
• Inactivation kinetics of I(to) were altered, with slower onset and recovery from inactivation after SNx.
• Action potential duration (APD(50)) was shortened at the left ventricular base in SNx rats, an effect reversed by 4-AP.

Conclusions:

• Abnormalities in the cardiac transient outward K(+) current (I(to)) are present in experimental renal failure.
• These I(to) abnormalities contribute to altered cardiac action potentials in renal failure.
• Further investigation is warranted to understand the role of these repolarization changes in arrhythmogenesis.