Acetylcholine, Ca2+ overload and oscillatory potentials in isolated ventricular myocytes

Area of Science:

• Cardiovascular Physiology
• Cellular Electrophysiology

Background:

• Overdrive pacing can induce calcium overload in ventricular myocytes.
• This overload may manifest as oscillatory potentials (Vos) and prolonged depolarization (Vex).

Purpose of the Study:

• To investigate the role of acetylcholine (ACh) in modulating overdrive-induced calcium overload events.
• To elucidate the underlying ionic mechanisms of these events.

Main Methods:

• Isolated guinea pig ventricular myocytes were subjected to overdrive pacing.
• Electrophysiological techniques including voltage clamp were employed.
• Pharmacological agents like acetylcholine, atropine, norepinephrine, caffeine, and quinacrine were used.

Main Results:

• Acetylcholine reduced or abolished overdrive-induced oscillatory potentials (Vos) and prolonged depolarization (Vex).
• Norepinephrine enhanced these events, but ACh antagonized this enhancement.
• Caffeine's effects varied with concentration, while quinacrine abolished both events.
• Voltage clamp indicated Ios involves electrogenic calcium extrusion, not increased conductance.

Conclusions:

• Acetylcholine antagonizes calcium overload effects in ventricular myocytes, both alone and during sympathetic enhancement.
• The mechanism of the oscillatory current (Ios) involves electrogenic calcium extrusion.