Two delayed rectifiers in guinea pig ventricular myocytes distinguished by tail current kinetics

Area of Science:

• Cardiovascular Physiology
• Electrophysiology
• Molecular Cardiology

Background:

• The delayed rectifier potassium current (IKr) in guinea pig ventricular myocytes is crucial for cardiac repolarization.
• Previous studies suggested IKr is a composite of multiple channel types.

Purpose of the Study:

• To pharmacologically and physiologically differentiate the components of the guinea pig ventricular myocyte delayed rectifier potassium current.
• To characterize the drug-sensitive and drug-insensitive components of IKr.

Main Methods:

• Whole-cell voltage clamp technique on single guinea pig ventricular myocytes.
• Analysis of tail current decay kinetics using biexponential fits (fast and slow components).
• Application of the benzenesulfonamide agent E-4031 to assess drug-specific current components.

Main Results:

• The fast decay phase of IKr tail current was selectively blocked by 5 microM E-4031, indicating a distinct channel type.
• The slow decay phase was present in both drug-sensitive and drug-insensitive currents.
• E-4031-sensitive current exhibited both fast and slow decay phases, suggesting a single drug-sensitive channel type.

Conclusions:

• The delayed rectifier potassium current in guinea pig ventricular myocytes is composed of at least two distinct channel types.
• The fast component of IKr tail current decay represents a distinct, E-4031-sensitive channel.
• These findings help define the characteristics of drug-sensitive and -insensitive potassium currents in cardiac myocytes.