Local cholinergic suppression of pacemaker activity in the rabbit sinoatrial node

Area of Science:

• Cardiovascular Physiology
• Electrophysiology
• Autonomic Nervous System

Background:

• The sinoatrial node (SAN) is the primary pacemaker of the heart.
• Vagal stimulation influences heart rate through the autonomic nervous system.
• Acetylcholine (ACh) is a key neurotransmitter in vagal signaling.

Purpose of the Study:

• To investigate the differential effects of vagal stimulation and ACh on primary and subsidiary pacemaker cells in the rabbit SAN.
• To determine the relationship between action potential upstroke velocity and cholinergic suppression of excitability.
• To explore the potential role of cholinergic effects in preventing reentrant tachycardias.

Main Methods:

• Microelectrode recordings from rabbit SAN pacemaker cells.
• Superfusion with acetylcholine (ACh) and transmural vagal stimulation.
• Assessment of action potential (AP) amplitude, upstroke velocity (dV/dt), and excitability.
• Pharmacological blockade with atropine.

Main Results:

• Both ACh and vagal stimulation lengthened atrial cycle length by 40-60%.
• Primary pacemaker cells exhibited suppressed AP amplitude and became inexcitable, while subsidiary cells and atrial cells remained excitable.
• Suppression of AP amplitude was concentration-dependent and inversely correlated with dV/dt, occurring in 93% of cells with dV/dt <3 V/s.
• Effects were reversible and abolished by atropine.

Conclusions:

• Cholinergic effects differ between primary and subsidiary SAN pacemaker cells, with primary cells becoming quiescent.
• Subsidiary pacemaker cells maintain excitability, potentially ensuring continuous cardiac rhythm.
• Quiescent regions in the SAN center may act as a functional barrier against reentrant tachycardias.