Ivabradine reduces heart rate in heart failure by blocking the If (funny) current. Which ion channels constitute the If current and where are they located?

• A Voltage-gated L-type calcium channels in the SA node that are activated by hyperpolarization
• B Transient receptor potential (TRP) channels conducting Na+ in atrial pacemaker cells
• C IKr (rapid delayed rectifier) K+ channels causing slow diastolic depolarization
• D HCN (hyperpolarization-activated cyclic nucleotide-gated) channels carrying mixed Na+/K+ inward current; located in sinoatrial node pacemaker cells ✓

Explanation

The If (funny) current is conducted through HCN channels (primarily HCN4 in the SA node), which open on hyperpolarization after repolarization and carry inward Na+ and K+ current, providing the depolarizing drive for phase 4 of the SA node action potential. Ivabradine selectively blocks these channels from the intracellular side in an open-state-dependent manner, reducing heart rate without affecting contractility or blood pressure. L-type Ca2+ channels contribute to phase 0 of SA node but are not HCN channels.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.