Evidence for two components of delayed rectifier K+ current in human ventricular myocytes

Area of Science:

• Cardiovascular Physiology
• Electrophysiology
• Molecular Cardiology

Background:

• Previous studies suggested minimal or absent delayed rectifier current (IK) in human ventricles, primarily IKr.
• Molecular data and IKr blocker effects indicate a more significant IK presence and role in human heart function.
• Cell isolation techniques can influence IK expression, necessitating careful experimental design.

Purpose of the Study:

• To assess the expression and functional significance of delayed rectifier potassium currents (IK) in human ventricular myocytes.
• To characterize the components of IK, including rapid (IKr) and slow (IKs) currents, and investigate the presence of ultrarapid (IKur).
• To determine the role of IK in human ventricular repolarization.

Main Methods:

• Electrophysiological recordings (voltage-clamp) of IK in human ventricular myocytes isolated from explanted hearts.
• Pharmacological characterization using E-4031 (IKr and IKs blocker) and indapamide (IKs selective inhibitor).
• Assessment of ultrarapid delayed rectifier current (IKur) using depolarizing prepulses and 4-aminopyridine.

Main Results:

• 94% of human ventricular myocytes exhibited time-dependent IK currents.
• E-4031 selectively suppressed IKr and IKs components, prolonging action potential duration, confirming a functional role for IK.
• IKur was detected in human atrial cells but not in ventricular myocytes.

Conclusions:

• Functionally significant IK, comprising IKr and IKs, is present in human ventricular cells.
• IKur is notably absent in human ventricular myocytes.
• These findings are critical for understanding human ventricular repolarization, arrhythmias, and drug actions.