{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:21:24Z","timestamp":1791336084977,"version":"4.3.1"},"reference-count":106,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2015,1,8]],"date-time":"2015-01-08T00:00:00Z","timestamp":1420675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004875","name":"DFG","doi-asserted-by":"publisher","award":["HE 6802\/2-1"],"award-info":[{"award-number":["HE 6802\/2-1"]}],"id":[{"id":"10.13039\/100004875","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u20134, 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.     <\/jats:p>","DOI":"10.3390\/ijms16011429","type":"journal-article","created":{"date-parts":[[2015,1,8]],"date-time":"2015-01-08T11:29:32Z","timestamp":1420716572000},"page":"1429-1447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["HCN Channels\u2014Modulators of Cardiac and Neuronal Excitability"],"prefix":"10.3390","volume":"16","author":[{"given":"Stefan","family":"Herrmann","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Experimentelle und Klinische Pharmakologie und Toxikologie,  Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Schnorr","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle und Klinische Pharmakologie und Toxikologie,  Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle und Klinische Pharmakologie und Toxikologie,  Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/31255","article-title":"A family of hyperpolarization-activated mammalian cation channels","volume":"393","author":"Ludwig","year":"1998","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0092-8674(00)81434-8","article-title":"Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain","volume":"93","author":"Santoro","year":"1998","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1093\/emboj\/18.9.2323","article-title":"Two pacemaker channels from human heart with profoundly different activation kinetics","volume":"18","author":"Ludwig","year":"1999","journal-title":"EMBO J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9391","DOI":"10.1073\/pnas.96.16.9391","article-title":"Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis","volume":"96","author":"Seifert","year":"1999","journal-title":"Proc. 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