HCN channels in behavior and neurological disease: Too hyper or not active enough?

Alan S. Lewis*, Dane M Chetkovich

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

56 Scopus citations


The roles of cells within the nervous system are based on their properties of excitability, which are in part governed by voltage-gated ion channels. HCN channels underlie the hyperpolarization-activated current, Ih, an important regulator of excitability and rhythmicity through control of basic membrane properties. Ih is present in multiple neuronal types and regions of the central nervous system, and changes in Ih alter cellular input-output properties and neuronal circuitry important for behavior such as learning and memory. Furthermore, the pathophysiology of neurological diseases of both the central and peripheral nervous system involves defects in excitability, rhythmicity, and signaling, and animal models of many of these disorders have implicated changes in HCN channels and Ih as critical for pathogenesis. In this review, we focus on recent research elucidating the role of HCN channels and Ih in behavior and disease. These studies have utilized knockout mice as well as animal models of disease to examine how Ih may be important in regulating learning and memory, sleep, and consciousness, as well as how misregulation of Ih may contribute to epilepsy, chronic pain, and other neurological disorders. This review will help guide future studies aimed at further understanding the function of this unique conductance in both health and disease of the mammalian brain.

Original languageEnglish (US)
Pages (from-to)357-367
Number of pages11
JournalMolecular and Cellular Neuroscience
Issue number2
StatePublished - Feb 1 2011


  • Epilepsy
  • HCN channel
  • Hyperpolarization-activated current
  • I
  • Learning and memory
  • Pain

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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