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January 15, 2013; 80 (3) Clinical Implications of Neuroscience Research

HCN channels

Function and clinical implications

Eduardo E. Benarroch
First published January 14, 2013, DOI: https://doi.org/10.1212/WNL.0b013e31827dec42
Eduardo E. Benarroch
From the Department of Neurology, Mayo Clinic, Rochester, MN.
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HCN channels
Function and clinical implications
Eduardo E. Benarroch
Neurology Jan 2013, 80 (3) 304-310; DOI: 10.1212/WNL.0b013e31827dec42

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The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels belong to the superfamily of pore-loop cation channels. In mammals, the HCN channel family comprises 4 members (HCN1–4) that are expressed in heart and nervous system. HCN channels are activated by membrane hyperpolarization, are permeable to Na+ and K+, and are constitutively open at voltages near the resting membrane potential. In many cases, activation is facilitated by direct interaction with cyclic nucleotides, particularly cyclic adenosine monophosphate (cAMP). The cation current through HCN channels is known as Ih; opening of HCN channels elicits membrane depolarization toward threshold for action potential generation, and reduces membrane resistance and thus the magnitude of excitatory and inhibitory postsynaptic potentials. HCN channels have a major role in controlling neuronal excitability, dendritic integration of synaptic potentials, synaptic transmission, and rhythmic oscillatory activity in individual neurons and neuronal networks. These channels participate in mechanisms of synaptic plasticity and memory, thalamocortical rhythms, and somatic sensation. Experimental evidence indicates that HCN channels may also contribute to mechanisms of epilepsy and pain. The physiologic functions of HCN channels and their implications for neurologic disorders have been recently reviewed.1–10

GLOSSARY

cAMP=
cyclic adenosine monophosphate;
CNBD=
cyclic nucleotide-binding domain;
DRG=
dorsal root ganglion;
EPSP=
excitatory postsynaptic potentials;
HCN=
hyperpolarization-activated cyclic nucleotide-gated;
LTP=
long-term potentiation;
PGE2=
prostaglandin E2;
PIP2=
phosphatidylinositol 4,5-bisphosphate;
SA=
sinoatrial

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  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • © 2013 American Academy of Neurology
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Letters: Rapid online correspondence

  • HCN function can be studied in human axons in vivo
    • David Burke, Neurologist, Department of Neurology, Royal Prince Alfred Hospital, The University of Sydney, Sydney, N.S.W. 2006david.burke@sydney.edu.au
    • David Burke, Sydney, Australia; James Howells, Sydney, Australia; Susan E. Tomlinson, Sydney, Australia
    Submitted January 29, 2013
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  • Article
    • GLOSSARY
    • HCN CHANNELS AND Ih CURRENT
    • PHYSIOLOGIC ROLE OF HCN CHANNELS AND Ih CURRENT
    • PHYSIOLOGIC IMPLICATIONS
    • CLINICAL CORRELATIONS
    • PERSPECTIVE
    • DISCLOSURE
    • Footnotes
    • REFERENCES
  • Figures & Data
  • Info & Disclosures
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