Acetylcholine (ACh) does not increase heart rate; rather, it acts to decrease it. This chemical messenger, or neurotransmitter, is one of the primary tools the body uses to manage the pace of the heart. ACh is responsible for the calming or inhibitory signals that promote a state of rest within the cardiovascular system.
Acetylcholine and the Vagus Nerve
Heart rate is constantly managed by the Autonomic Nervous System (ANS), which operates without conscious thought. The ANS is divided into two main branches: the Sympathetic Nervous System (“fight or flight”) and the Parasympathetic Nervous System (“rest and digest”). Acetylcholine is the chief neurotransmitter used by the parasympathetic branch to communicate with the heart.
The Vagus nerve (tenth cranial nerve, CN X) carries the slowing signal. This nerve is the longest in the autonomic system, carrying signals from the brainstem to organs, including the heart. The right vagus nerve primarily innervates the heart’s natural pacemaker. When the body is at rest, the Vagus nerve releases ACh directly onto the heart muscle to slow its rhythm.
The Cellular Mechanism of Slowing Heart Rate
Acetylcholine exerts its effect by targeting the Sinoatrial (SA) node, a cluster of specialized cells in the upper right chamber of the heart. The SA node acts as the heart’s primary pacemaker, spontaneously generating electrical impulses that determine the heart rate. ACh binds to specific protein structures on these cells called Muscarinic type 2 (M2) receptors.
Activation of the M2 receptor triggers a signal inside the cell involving a G-protein complex. This complex directly causes potassium ion channels to open, allowing positively charged potassium ions to flow out of the cell. This outward movement of positive charge makes the inside of the cell more negative, a process known as hyperpolarization.
Hyperpolarization makes the pacemaker cell less excitable and increases the time required for the cell to reach the threshold needed to fire the next impulse. By slowing this rate of spontaneous depolarization, ACh effectively reduces the frequency of heartbeats. This mechanism allows the nervous system to maintain a stable, lower heart rate during periods of calm.
Contrast: How the Heart Speeds Up
The heart speeds up through the opposing action of the Sympathetic Nervous System, activated by physical activity or stress. This system uses different chemical messengers, primarily the neurotransmitter Norepinephrine and the hormone Epinephrine (Adrenaline). These chemicals are released onto the same SA node pacemaker cells targeted by acetylcholine.
Norepinephrine and Epinephrine bind to a different set of receptors called Beta-1 adrenergic receptors. Activation of these receptors initiates a signal cascade that increases the flow of other ions, most notably calcium, into the pacemaker cell. This influx of positive calcium ions increases the excitability of the SA node cells.
The action of the sympathetic system steepens the slope of the pacemaker potential, meaning the cells reach their firing threshold more quickly. This accelerated rate of firing results in an increased heart rate and a stronger force of contraction. The heart is constantly regulated by the balanced push-and-pull of these two opposing systems.