Calcium-sensitive and insensitive transient outward current in rabbit ventricular myocytes

Area of Science:

• Cardiac Electrophysiology
• Ion Channel Physiology
• Molecular Cardiology

Background:

• Ventricular myocytes exhibit transient outward current (Ito) crucial for cardiac action potential repolarization.
• Understanding the distinct components of Ito and their physiological roles is essential for comprehending cardiac function.
• Previous studies suggested heterogeneity within Ito, but specific characterization remained incomplete.

Purpose of the Study:

• To differentiate and characterize the components of transient outward current (Ito) in rabbit ventricular myocytes.
• To elucidate the ionic basis and physiological significance of calcium-insensitive (It) and calcium-sensitive (IK,Ca) Ito.
• To determine the roles of It and IK,Ca in ventricular repolarization under varying heart rates.

Main Methods:

• Whole-cell voltage-clamp recordings were performed on isolated rabbit ventricular myocytes.
• Pharmacological agents (4-aminopyridine, caffeine) and ionic manipulations (Ca2+, Sr2+, EGTA) were used to dissect current components.
• Analysis of voltage-dependence, inactivation kinetics, and reversal potentials characterized the identified currents.

Main Results:

• Two distinct Ito components were identified: a calcium-insensitive It and a calcium-sensitive IK,Ca.
• It exhibited voltage- and time-dependent inactivation and was sensitive to external potassium concentration.
• IK,Ca was dependent on intracellular calcium, involving influx and sarcoplasmic reticulum release, and showed different kinetics than It.

Conclusions:

• Rabbit ventricular myocytes possess distinct calcium-insensitive (It) and calcium-sensitive (IK,Ca) transient outward currents.
• It contributes to ventricular repolarization at slow heart rates, while IK,Ca is important at fast heart rates.
• This detailed characterization provides insights into the complex mechanisms governing cardiac repolarization.