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Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization. Cyclic nucleotides enhance HCN channel activity by affecting the voltage dependence of channel activation (Biel et al. 2009).
A cation current that slowly activates upon membrane hyperpolarization was detected in a variety of excitable cells including neurons and cardiac pacemaker cells in the late 1970s and early 1980s. This current is inwardly directed at the physiological resting membrane potentials of most cells and is carried by Na+ and K+ ions and, hence, depolarizes the cell membrane. Additionally, cyclic adenosine monophosphate (cAMP) was found to facilitate current activation in a direct, PKA-independent manner. Because of these unique biophysical properties, this current was termed funny current (If) in the heart or hyperpolarization-activated current (Ih) in the brain.
HCN channels represent the molecular correlate of the Ih/If...
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