Voltage- and time-dependent block of iK1 underlying Ba2+-induced ventricular automaticity

Area of Science:

• Cardiology
• Electrophysiology
• Cellular Biology

Background:

• Cardiac automaticity is crucial for heart rhythm.
• Barium ions (Ba2+) are known to affect ion channel function.
• The precise mechanism of Ba2+-induced automaticity in ventricular myocytes requires elucidation.

Purpose of the Study:

• To investigate the underlying mechanism of Ba2+-induced automaticity in isolated guinea pig ventricular myocytes.
• To determine the role of inward currents and K+ channels in Ba2+-induced rhythmic activity.

Main Methods:

• Whole-cell patch-clamp electrophysiology was used to record ionic currents and action potentials.
• Voltage-clamp experiments were performed to study the effect of Ba2+ on ion currents.
• Mathematical modeling and simulation were employed to test hypotheses.

Main Results:

• Barium ions (Ba2+) induced spontaneous action potential firing in ventricular myocytes.
• This automaticity persisted despite blockade of Na+ and Ca2+ channels, and removal of external Na+ and Ca2+.
• Voltage-clamp studies demonstrated that Ba2+ selectively and potently blocked the inward rectifier K+ current (iK1) in a voltage- and time-dependent manner.
• A mathematical model incorporating Ba2+-block of iK1 accurately reproduced the observed automatic activity.

Conclusions:

• The voltage- and time-dependent block of the inward rectifier K+ current (iK1) by Ba2+ is a key mechanism responsible for inducing automaticity in isolated ventricular cells.
• This finding provides significant insight into the role of iK1 in cardiac rhythmicity and the effects of divalent cations.