PUBLICATION
Popeye domain containing proteins modulate the voltage-gated cardiac sodium channel Nav1.5
- Authors
- Rinné, S., Kiper, A.K., Jacob, R., Ortiz-Bonnin, B., Schindler, R.F.R., Fischer, S., Komadowski, M., De Martino, E., Schäfer, M.K., Cornelius, T., Fabritz, L., Helker, C.S.M., Brand, T., Decher, N.
- ID
- ZDB-PUB-240501-4
- Date
- 2024
- Source
- iScience 27: 109696109696 (Journal)
- Registered Authors
- Brand, Thomas, Fischer, Sabine, Helker, Christian
- Keywords
- Biochemistry, Molecular biology, Physiology
- MeSH Terms
- none
- PubMed
- 38689644 Full text @ iScience
Abstract
Popeye domain containing (POPDC) proteins are predominantly expressed in the heart and skeletal muscle, modulating the K2P potassium channel TREK-1 in a cAMP-dependent manner. POPDC1 and POPDC2 variants cause cardiac conduction disorders with or without muscular dystrophy. Searching for POPDC2-modulated ion channels using a functional co-expression screen in Xenopus oocytes, we found POPDC proteins to modulate the cardiac sodium channel Nav1.5. POPDC proteins downregulate Nav1.5 currents in a cAMP-dependent manner by reducing the surface expression of the channel. POPDC2 and Nav1.5 are both expressed in different regions of the murine heart and consistently POPDC2 co-immunoprecipitates with Nav1.5 from native cardiac tissue. Strikingly, the knock-down of popdc2 in embryonic zebrafish caused an increased upstroke velocity and overshoot of cardiac action potentials. The POPDC modulation of Nav1.5 provides a new mechanism to regulate cardiac sodium channel densities under sympathetic stimulation, which is likely to have a functional impact on cardiac physiology and inherited arrhythmias.
Genes / Markers
Figure Gallery (6 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping