RT Journal Article
SR Electronic
T1 The Hyperpolarization-Activated Cyclic Nucleotide–Gated Channels: from Biophysics to Pharmacology of a Unique Family of Ion Channels
JF Pharmacological Reviews
JO Pharmacol Rev
FD American Society for Pharmacology and Experimental Therapeutics
SP 354
OP 395
DO 10.1124/pr.117.014035
VO 69
IS 4
A1 Sartiani, Laura
A1 Mannaioni, Guido
A1 Masi, Alessio
A1 Novella Romanelli, Maria
A1 Cerbai, Elisabetta
A2 Garland, Christopher J.
YR 2017
UL http://pharmrev.aspetjournals.org/content/69/4/354.abstract
AB Hyperpolarization-activated, cyclic nucleotide–gated (HCN) channels are important members of the voltage-gated pore loop channels family. They show unique features: they open at hyperpolarizing potential, carry a mixed Na/K current, and are regulated by cyclic nucleotides. Four different isoforms have been cloned (HCN1–4) that can assemble to form homo- or heterotetramers, characterized by different biophysical properties. These proteins are widely distributed throughout the body and involved in different physiologic processes, the most important being the generation of spontaneous electrical activity in the heart and the regulation of synaptic transmission in the brain. Their role in heart rate, neuronal pacemaking, dendritic integration, learning and memory, and visual and pain perceptions has been extensively studied; these channels have been found also in some peripheral tissues, where their functions still need to be fully elucidated. Genetic defects and altered expression of HCN channels are linked to several pathologies, which makes these proteins attractive targets for translational research; at the moment only one drug (ivabradine), which specifically blocks the hyperpolarization-activated current, is clinically available. This review discusses current knowledge about HCN channels, starting from their biophysical properties, origin, and developmental features, to (patho)physiologic role in different tissues and pharmacological modulation, ending with their present and future relevance as drug targets.