HCN channels, also known as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, are a subfamily of ion channels activated by the cell membrane’s hyperpolarisation. They are primarily responsible for generating “pacemaker” currents, which are critical for regulating heart rate and other rhythmic activities in the body. They are activated by intracellular cyclic nucleotides, such as cAMP and cGMP, and are blocked by intracellular acidosis.

HCN channels are found in various tissues, including the heart, brain and endocrine cells. They play a critical role in regulating heart rate, and mutations in HCN channels have been linked to various cardiac arrhythmias and heart diseases. They are also involved in regulating the rhythmicity of neurons in the brain and the regulation of insulin secretion in endocrine cells.

Therapeutic targeting of HCN channels is an active area of research, and HCN channel blockers have been proposed as a new class of anti-arrhythmic drugs. Additionally, HCN channel modulators have been proposed as potential therapies for brain disorders such as epilepsy, sleep disorders and depression.