---
_id: '6868'
abstract:
- lang: eng
  text: "Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels control
    electrical rhythmicity and excitability in the heart and brain, but the function
    of HCN channels at the subcellular level in axons remains poorly understood. Here,
    we show that the action potential conduction velocity in both myelinated and unmyelinated
    central axons can be bidirectionally modulated by a HCN channel blocker, cyclic
    adenosine monophosphate (cAMP), and neuromodulators. Recordings from mouse cerebellar
    mossy fiber boutons show that HCN channels ensure reliable high-frequency firing
    and are strongly modulated by cAMP (EC50 40 mM; estimated endogenous cAMP concentration
    13 mM). In addition, immunogold-electron microscopy revealed HCN2 as the dominating
    subunit in cerebellar mossy fibers. Computational modeling indicated that HCN2
    channels control conduction velocity primarily by altering the resting membrane
    potential\r\nand are associated with significant metabolic costs. These results
    suggest that the cAMP-HCN pathway provides neuromodulators with an opportunity
    to finely tune energy consumption and temporal delays across axons in the brain."
article_number: e42766
article_processing_charge: No
article_type: original
author:
- first_name: Niklas
  full_name: Byczkowicz, Niklas
  last_name: Byczkowicz
- first_name: Abdelmoneim
  full_name: Eshra, Abdelmoneim
  last_name: Eshra
- first_name: Jacqueline-Claire
  full_name: Montanaro-Punzengruber, Jacqueline-Claire
  id: 3786AB44-F248-11E8-B48F-1D18A9856A87
  last_name: Montanaro-Punzengruber
- first_name: Andrea
  full_name: Trevisiol, Andrea
  last_name: Trevisiol
- first_name: Johannes
  full_name: Hirrlinger, Johannes
  last_name: Hirrlinger
- first_name: Maarten Hp
  full_name: Kole, Maarten Hp
  last_name: Kole
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Stefan
  full_name: Hallermann, Stefan
  last_name: Hallermann
citation:
  ama: Byczkowicz N, Eshra A, Montanaro-Punzengruber J-C, et al. HCN channel-mediated
    neuromodulation can control action potential velocity and fidelity in central
    axons. <i>eLife</i>. 2019;8. doi:<a href="https://doi.org/10.7554/eLife.42766">10.7554/eLife.42766</a>
  apa: Byczkowicz, N., Eshra, A., Montanaro-Punzengruber, J.-C., Trevisiol, A., Hirrlinger,
    J., Kole, M. H., … Hallermann, S. (2019). HCN channel-mediated neuromodulation
    can control action potential velocity and fidelity in central axons. <i>ELife</i>.
    eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.42766">https://doi.org/10.7554/eLife.42766</a>
  chicago: Byczkowicz, Niklas, Abdelmoneim Eshra, Jacqueline-Claire Montanaro-Punzengruber,
    Andrea Trevisiol, Johannes Hirrlinger, Maarten Hp Kole, Ryuichi Shigemoto, and
    Stefan Hallermann. “HCN Channel-Mediated Neuromodulation Can Control Action Potential
    Velocity and Fidelity in Central Axons.” <i>ELife</i>. eLife Sciences Publications,
    2019. <a href="https://doi.org/10.7554/eLife.42766">https://doi.org/10.7554/eLife.42766</a>.
  ieee: N. Byczkowicz <i>et al.</i>, “HCN channel-mediated neuromodulation can control
    action potential velocity and fidelity in central axons,” <i>eLife</i>, vol. 8.
    eLife Sciences Publications, 2019.
  ista: Byczkowicz N, Eshra A, Montanaro-Punzengruber J-C, Trevisiol A, Hirrlinger
    J, Kole MH, Shigemoto R, Hallermann S. 2019. HCN channel-mediated neuromodulation
    can control action potential velocity and fidelity in central axons. eLife. 8,
    e42766.
  mla: Byczkowicz, Niklas, et al. “HCN Channel-Mediated Neuromodulation Can Control
    Action Potential Velocity and Fidelity in Central Axons.” <i>ELife</i>, vol. 8,
    e42766, eLife Sciences Publications, 2019, doi:<a href="https://doi.org/10.7554/eLife.42766">10.7554/eLife.42766</a>.
  short: N. Byczkowicz, A. Eshra, J.-C. Montanaro-Punzengruber, A. Trevisiol, J. Hirrlinger,
    M.H. Kole, R. Shigemoto, S. Hallermann, ELife 8 (2019).
date_created: 2019-09-15T22:00:43Z
date_published: 2019-09-09T00:00:00Z
date_updated: 2026-04-03T09:40:28Z
day: '09'
ddc:
- '570'
department:
- _id: RySh
doi: 10.7554/eLife.42766
external_id:
  isi:
  - '000485663900001'
file:
- access_level: open_access
  checksum: c350b7861ef0fb537cae8a3232aec016
  content_type: application/pdf
  creator: dernst
  date_created: 2019-09-16T13:14:33Z
  date_updated: 2020-07-14T12:47:42Z
  file_id: '6880'
  file_name: 2019_eLife_Byczkowicz.pdf
  file_size: 4008137
  relation: main_file
file_date_updated: 2020-07-14T12:47:42Z
has_accepted_license: '1'
intvolume: '         8'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: HCN channel-mediated neuromodulation can control action potential velocity
  and fidelity in central axons
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 8
year: '2019'
...