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Gating mechanism of hyperpolarization-activated HCN pacemaker channels

Author

Listed:
  • Rosamary Ramentol

    (University of Miami)

  • Marta E. Perez

    (University of Miami)

  • H. Peter Larsson

    (University of Miami)

Abstract

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are essential for rhythmic activity in the heart and brain, and mutations in HCN channels are linked to heart arrhythmia and epilepsy. HCN channels belong to the family of voltage-gated K+ (Kv) channels. However, why HCN channels are activated by hyperpolarization whereas Kv channels are activated by depolarization is not clear. Here we reverse the voltage dependence of HCN channels by mutating only two residues located at the interface between the voltage sensor and the pore domain such that the channels now open upon depolarization instead of hyperpolarization. Our data indicate that what determines whether HCN channels open by hyperpolarizations or depolarizations are small differences in the energies of the closed and open states, due to different interactions between the voltage sensor and the pore in the different channels.

Suggested Citation

  • Rosamary Ramentol & Marta E. Perez & H. Peter Larsson, 2020. "Gating mechanism of hyperpolarization-activated HCN pacemaker channels," Nature Communications, Nature, vol. 11(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15233-9
    DOI: 10.1038/s41467-020-15233-9
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    Cited by:

    1. Lucas J. Handlin & Natalie L. Macchi & Nicolas L. A. Dumaire & Lyuba Salih & Erin N. Lessie & Kyle S. McCommis & Aubin Moutal & Gucan Dai, 2024. "Membrane lipid nanodomains modulate HCN pacemaker channels in nociceptor DRG neurons," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Lucas J. Handlin & Gucan Dai, 2023. "Direct regulation of the voltage sensor of HCN channels by membrane lipid compartmentalization," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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