Ionic basis of depressed automaticity and conduction by acetylcholine in rabbit AV node

Area of Science:

• Electrophysiology
• Cardiac Physiology
• Ion Channel Function

Background:

• The atrioventricular (AV) node plays a critical role in regulating cardiac rhythm.
• Acetylcholine (ACh) is known to exert negative chronotropic and dromotropic effects on the AV node.
• The precise ionic mechanisms underlying these effects require detailed investigation.

Purpose of the Study:

• To elucidate the ionic mechanisms responsible for acetylcholine's (ACh) negative chronotropic and dromotropic effects on the AV node.
• To characterize the properties of the ACh-sensitive outward potassium current (IACh).

Main Methods:

• Experiments were conducted on rabbit AV node preparations.
• Utilized double-microelectrode techniques for current-clamp and voltage-clamp recordings.
• Analyzed changes in membrane potential, resistance, space constant, time constant, and ionic currents.

Main Results:

• ACh (10(-6) M) induced hyperpolarization, decreased membrane resistance, and reduced space and time constants.
• ACh inhibited the slow inward current by 11% and activated an outward K+ current (IACh).
• IACh exhibited inward rectification, relaxation, and K+ selectivity, with its reversal potential dependent on external K+ concentration.

Conclusions:

• The study identifies IACh as a K+-selective current contributing to AV node hyperpolarization and slowed conduction.
• IACh inhibits phase 4 and phase 0 depolarizations, reducing electronic current spread within the AV node.
• The negative chronotropic and dromotropic actions of ACh are likely augmented by the reduction in the slow inward current.