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A family of hyperpolarization-activated mammalian cation channels

Author

Listed:
  • Andreas Ludwig

    (Institut für Pharmakologie und Toxikologie, Technische Universität München)

  • Xiangang Zong

    (Institut für Pharmakologie und Toxikologie, Technische Universität München)

  • Michael Jeglitsch

    (Institut für Pharmakologie und Toxikologie, Technische Universität München)

  • Franz Hofmann

    (Institut für Pharmakologie und Toxikologie, Technische Universität München)

  • Martin Biel

    (Institut für Pharmakologie und Toxikologie, Technische Universität München)

Abstract

Pacemaker activity of spontaneously active neurons1,2,3 and heart cells4,5,6 is controlled by a depolarizing, mixed Na+/K+ current, named Ih (or If in the sinoatrial node of the heart)1,4. This current is activated on hyperpolarization of the plasma membrane. In addition to depolarizing pacemaker cells, Ih is involved in determining the resting membrane potential of neurons1,2 and provides a mechanism to limit hyperpolarizing currents in these cells7,8,9. Hormones and neurotransmitters that induce a rise in cyclic AMP levels increase Ih by a mechanism that is independent of protein phosphorylation, and which involves direct binding of the cyclic nucleotide to the channel that mediates Ih10,11,12,13. Here we report the molecular cloning and functional expression of the gene encoding a hyperpolarization-activated cation channel (HAC1) that is present in brain and heart. This channel exhibits the general properties of Ih channels. We have also identified full-length sequences of two related channels, HAC2 and HAC3, that are specifically expressed in the brain, indicating the existence of a family of hyperpolarization-activated cation channels.

Suggested Citation

  • Andreas Ludwig & Xiangang Zong & Michael Jeglitsch & Franz Hofmann & Martin Biel, 1998. "A family of hyperpolarization-activated mammalian cation channels," Nature, Nature, vol. 393(6685), pages 587-591, June.
    • Handle: RePEc:nat:nature:v:393:y:1998:i:6685:d:10.1038_31255
    DOI: 10.1038/31255
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    Cited by:

    1. Verena Burtscher & Jonathan Mount & Jian Huang & John Cowgill & Yongchang Chang & Kathleen Bickel & Jianhan Chen & Peng Yuan & Baron Chanda, 2024. "Structural basis for hyperpolarization-dependent opening of human HCN1 channel," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Sabine Hummert & Susanne Thon & Thomas Eick & Ralf Schmauder & Eckhard Schulz & Klaus Benndorf, 2018. "Activation gating in HCN2 channels," PLOS Computational Biology, Public Library of Science, vol. 14(3), pages 1-18, March.

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