A quantitative description of the E-4031-sensitive repolarization current in rabbit ventricular myocytes

Area of Science:

• Cardiovascular Physiology
• Ion Channel Biophysics
• Cardiac Electrophysiology

Background:

• The rapid component of the delayed rectifier potassium current (IKr) is crucial for cardiac repolarization.
• Previous studies on IKr kinetics have primarily used guinea pig models.

Purpose of the Study:

• To characterize the kinetic and ion transfer properties of E-4031-sensitive IKr in rabbit ventricular myocytes.
• To investigate the relationship between IKr gating kinetics and activation curves.
• To resolve the observed gating current paradox.

Main Methods:

• Isolation of single ventricular myocytes from rabbit hearts.
• Measurement of E-4031-sensitive repolarization current (IKr) using electrophysiological techniques.
• Analysis of IKr kinetic properties, including time constants and voltage dependence.
• Examination of the current-voltage (I-V) relationship and reversal potential.

Main Results:

• IKr exhibited a significantly slower maximum time constant (0.8 s at 33-34°C) compared to previous reports.
• A novel relationship was observed between the bell-shaped voltage dependence of kinetics and the sigmoidal activation curve, indicating a gating current paradox.
• Strong inward rectification was present in the IKr current-voltage relation, with current becoming negligible at +30 mV.
• The reversal potential for IKr was approximately +15 mV more positive than the potassium equilibrium potential.

Conclusions:

• Rabbit ventricular IKr possesses distinct kinetic and gating properties compared to guinea pig.
• The observed gating current paradox suggests complexities in IKr channel gating not explained by simple models.
• Inward rectification and the positive shift in reversal potential influence the role of IKr during the action potential plateau and repolarization.