Parasympathetic Action on Heart Pacemaker Cells

Parasympathetic nerves regulate heart rate primarily through the release of the neurotransmitter acetylcholine (ACh).

Mechanism of Acetylcholine Action

• Receptor Binding: Acetylcholine binds to muscarinic M2 receptors, which are G protein-coupled receptors (GPCRs), located on the surface of heart pacemaker cells.
• G Protein Activation: This binding event activates an associated inhibitory G protein (typically Gᵢ/G₀).
• Signal Transduction: The activated G protein then initiates intracellular signaling cascades. It inhibits the enzyme adenylyl cyclase, which reduces the production of cyclic AMP (cAMP). Importantly, it also directly modulates ion channels: it promotes the opening of potassium (K⁺) channels (specifically GIRK channels) and inhibits the opening of calcium (Ca²⁺) channels.
• Effect on Pacemaker Cells: The increased outflow of K⁺ ions and decreased influx of Ca²⁺ ions cause hyperpolarization of the cell membrane and slow down the rate of spontaneous depolarization.
• Heart Rate Regulation: Consequently, the frequency of action potentials generated by the pacemaker cells decreases, leading to a reduction in the heart rate.

Therefore, acetylcholine released by parasympathetic nerves binds to GPCRs and activates G proteins to slow the heart rate.

This corresponds to Option 1.