Which of the following would produce a negative chronotropic effect?

Which of the following would produce a negative chronotropic effect?

• A. Parasympathetic stimulation.
• B. Norepinephrine release.
• C. Beta-adrenergic stimulation.
• D. Epinephrine release.

Answer: (A)

Negative chronotropic effect means slowing the heart rate by reducing the firing rate of the SA node. Parasympathetic stimulation achieves this by releasing acetylcholine onto M2 muscarinic receptors in the SA and AV nodes. Activation of these receptors opens potassium channels and inhibits adenylate cyclase via Gi, lowering cAMP. The result is a slower pacemaker potential, decreased funny current and calcium entry, and thus slower automaticity and AV conduction. In contrast, norepinephrine or epinephrine release and beta-adrenergic stimulation boost heart rate by activating beta-1 receptors (through a Gs pathway), increasing cAMP, and enhancing inward currents that speed up the pacemaker potential and conduction. So those inputs produce a positive chronotropic effect, while parasympathetic input specifically produces the negative chronotropic effect.

Negative chronotropic effect means slowing the heart rate by reducing the firing rate of the SA node. Parasympathetic stimulation achieves this by releasing acetylcholine onto M2 muscarinic receptors in the SA and AV nodes. Activation of these receptors opens potassium channels and inhibits adenylate cyclase via Gi, lowering cAMP. The result is a slower pacemaker potential, decreased funny current and calcium entry, and thus slower automaticity and AV conduction.

In contrast, norepinephrine or epinephrine release and beta-adrenergic stimulation boost heart rate by activating beta-1 receptors (through a Gs pathway), increasing cAMP, and enhancing inward currents that speed up the pacemaker potential and conduction. So those inputs produce a positive chronotropic effect, while parasympathetic input specifically produces the negative chronotropic effect.