title: HCN channels--modulators of cardiac and neuronal excitability.
abstract: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a family of cation channels activated by hyperpolarized membrane potentials and stimulated by intracellular cyclic nucleotides. The four members of this family, HCN1-4, show distinct biophysical properties which are most evident in the kinetics of activation and deactivation, the sensitivity towards cyclic nucleotides and the modulation by tyrosine phosphorylation. The four isoforms are differentially expressed in various excitable tissues. This review will mainly focus on recent insights into the functional role of the channels apart from their classic role as pacemakers. The importance of HCN channels in the cardiac ventricle and ventricular hypertrophy will be discussed. In addition, their functional significance in the peripheral nervous system and nociception will be examined. The data, which are mainly derived from studies using transgenic mice, suggest that HCN channels contribute significantly to cellular excitability in these tissues. Remarkably, the impact of the channels is clearly more pronounced in pathophysiological states including ventricular hypertrophy as well as neural inflammation and neuropathy suggesting that HCN channels may constitute promising drug targets in the treatment of these conditions. This perspective as well as the current therapeutic use of HCN blockers will also be addressed.
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany. Stefan.Herrmann@pharmakologie.uni-erlangen.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Herrmann
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany. Sabine.Schnorr@pharmakologie.uni-erlangen.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schnorr
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany. Andreas.Ludwig@pharmakologie.uni-erlangen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ludwig
mesh_terms: D000200:Action Potentials; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology; D002317:Cardiovascular Agents / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000188:drug therapy; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: D002317:Cardiovascular Agents; D054815:Cyclic Nucleotide-Gated Cation Channels; D020033:Protein Isoforms