The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the pacemaker 'funny current' (If) in the SA node is activated by which condition?
- A Depolarization to +20 mV combined with intracellular Ca²⁺ rise
- B Hyperpolarization below –60 mV and increased cAMP binding to the channel ✓
- C Decreased intracellular cAMP following parasympathetic stimulation
- D Elevated extracellular K⁺ concentration reversing the K⁺ equilibrium potential
Explanation
HCN channels (primarily HCN4 in human SA node) open on hyperpolarization below approximately –50 to –60 mV and carry a mixed Na⁺/K⁺ inward current (If) that gradually depolarizes the cell toward threshold. Sympathetic stimulation raises cAMP, which binds directly to the HCN channel CNBD domain, shifting its activation curve to less negative voltages (faster firing). Parasympathetic stimulation reduces cAMP, shifts activation to more negative voltages, and slows heart rate. Ivabradine specifically blocks HCN channels to reduce heart rate without affecting contractility.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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Written and medically reviewed by the StethoPrep medical team.