Characterization of the HCN Interaction Partner TRIP8b/PEX5R in the Intracardiac Nervous System of TRIP8b-Deficient and Wild-Type Mice
| Autor: | Nikolaj Klöcker, Christian Meyer, Nadine Erlenhardt, Hanna Bräuninger, Christiane Jungen, Dane M. Chetkovich, Ehsan Amin, Ulrike Pape, Diana Lindner, Andrea Mölders, Katharina Scherschel |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Nervous system Refractory period QH301-705.5 Gene Expression In situ hybridization 030204 cardiovascular system & hematology TRIP8b Catalysis Article Inorganic Chemistry Peroxins HCN channels 03 medical and health sciences Mice 0302 clinical medicine medicine Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Animals Protein Interaction Maps RNA Messenger Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy Cardiac electrophysiology Chemistry Myocardium Organic Chemistry autonomic nervous system Membrane Proteins Heart General Medicine Atrioventricular node Computer Science Applications Cell biology Mice Inbred C57BL Autonomic nervous system Electrophysiology 030104 developmental biology medicine.anatomical_structure Electrical conduction system of the heart cardiac electrophysiology Gene Deletion |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 9 International Journal of Molecular Sciences, Vol 22, Iss 4772, p 4772 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22094772 |
| Popis: | The tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b/PEX5R) is an interaction partner and auxiliary subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are key for rhythm generation in the brain and in the heart. Since TRIP8b is expressed in central neurons but not in cardiomyocytes, the TRIP8b-HCN interaction has been studied intensely in the brain, but is deemed irrelevant in the cardiac conduction system. Still, to date, TRIP8b has not been studied in the intrinsic cardiac nervous system (ICNS), a neuronal network located within epicardial fat pads. In vitro electrophysiological studies revealed that TRIP8b-deficient mouse hearts exhibit increased atrial refractory and atrioventricular nodal refractory periods, compared to hearts of wild-type littermates. Meanwhile, heart rate, sino-nodal recovery time, and ventricular refractory period did not differ between genotypes. Trip8b mRNA was detected in the ICNS by quantitative polymerase chain reaction. RNAscope in situ hybridization confirmed Trip8b localization in neuronal somata and nerve fibers. Additionally, we found a very low amount of mRNAs in the sinus node and atrioventricular node, most likely attributable to the delicate fibers innervating the conduction system. In contrast, TRIP8b protein was not detectable. Our data suggest that TRIP8b in the ICNS may play a role in the modulation of atrial electrophysiology beyond HCN-mediated sino-nodal control of the heart. |
| Databáze: | OpenAIRE |
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