Nature Communications (Nov 2020)
cAMP-dependent regulation of HCN4 controls the tonic entrainment process in sinoatrial node pacemaker cells
- Stefanie Fenske,
- Konstantin Hennis,
- René D. Rötzer,
- Verena F. Brox,
- Elvir Becirovic,
- Andreas Scharr,
- Christian Gruner,
- Tilman Ziegler,
- Verena Mehlfeld,
- Jaclyn Brennan,
- Igor R. Efimov,
- Audrys G. Pauža,
- Markus Moser,
- Carsten T. Wotjak,
- Christian Kupatt,
- Rasmus Gönner,
- Rai Zhang,
- Henggui Zhang,
- Xiangang Zong,
- Martin Biel,
- Christian Wahl-Schott
Affiliations
- Stefanie Fenske
- Center for Integrated Protein Science (CIPS-M) and Center for Drug Research, Department of Pharmacy, Ludwig-Maximilians-Universität München
- Konstantin Hennis
- Center for Integrated Protein Science (CIPS-M) and Center for Drug Research, Department of Pharmacy, Ludwig-Maximilians-Universität München
- René D. Rötzer
- Center for Integrated Protein Science (CIPS-M) and Center for Drug Research, Department of Pharmacy, Ludwig-Maximilians-Universität München
- Verena F. Brox
- Center for Integrated Protein Science (CIPS-M) and Center for Drug Research, Department of Pharmacy, Ludwig-Maximilians-Universität München
- Elvir Becirovic
- Center for Integrated Protein Science (CIPS-M) and Center for Drug Research, Department of Pharmacy, Ludwig-Maximilians-Universität München
- Andreas Scharr
- Center for Integrated Protein Science (CIPS-M) and Center for Drug Research, Department of Pharmacy, Ludwig-Maximilians-Universität München
- Christian Gruner
- Center for Integrated Protein Science (CIPS-M) and Center for Drug Research, Department of Pharmacy, Ludwig-Maximilians-Universität München
- Tilman Ziegler
- German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance
- Verena Mehlfeld
- Center for Integrated Protein Science (CIPS-M) and Center for Drug Research, Department of Pharmacy, Ludwig-Maximilians-Universität München
- Jaclyn Brennan
- Department of Biomedical Engineering, George Washington University
- Igor R. Efimov
- Department of Biomedical Engineering, George Washington University
- Audrys G. Pauža
- Institute of Anatomy, Lithuanian University of Health Sciences, LT
- Markus Moser
- Max Planck Institute of Biochemistry, Department of Molecular Medicine
- Carsten T. Wotjak
- Max Planck Institute of Psychiatry, Research Group Neuronal Plasticity
- Christian Kupatt
- German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance
- Rasmus Gönner
- Center for Integrated Protein Science (CIPS-M) and Center for Drug Research, Department of Pharmacy, Ludwig-Maximilians-Universität München
- Rai Zhang
- Department of Aerospace Engineering, University of Bristol
- Henggui Zhang
- Department of Physics and Astronomy, The University of Manchester
- Xiangang Zong
- Center for Integrated Protein Science (CIPS-M) and Center for Drug Research, Department of Pharmacy, Ludwig-Maximilians-Universität München
- Martin Biel
- Center for Integrated Protein Science (CIPS-M) and Center for Drug Research, Department of Pharmacy, Ludwig-Maximilians-Universität München
- Christian Wahl-Schott
- Hannover Medical School, Institute for Neurophysiology
- DOI
- https://doi.org/10.1038/s41467-020-19304-9
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 22
Abstract
The involvement of cAMP-dependent regulation of HCN4 in the chronotropic heart rate response is a matter of debate. Here the authors use a knockin mouse model expressing cAMP-insensitive HCN4 channels to discover an inhibitory nonfiring cell pool in the sinoatrial node and a tonic and mutual interaction between firing and nonfiring pacemaker cells that is controlled by cAMP-dependent regulation of HCN4, with implications in chronotropic heart rate responses.
