A Possible Role of Tetrodotoxin-Sensitive Na + Channels for Oxidation-Induced Late Na + Currents in Cardiomyocytes.
Anja SchneiderAxel HageInês Carvalheira Arnaut Pombeiro SteinNils KriedemannRobert ZweigerdtTabea C FrickePublished in: International journal of molecular sciences (2024)
An accumulation of reactive oxygen species (ROS) in cardiomyocytes can induce pro-arrhythmogenic late Na + currents by removing the inactivation of voltage-gated Na + channels including the tetrodotoxin (TTX)-resistant cardiac α-subunit Nav1.5 as well as TTX-sensitive α-subunits like Nav1.2 and Nav1.3. Here, we explored oxidant-induced late Na + currents in mouse cardiomyocytes and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as well as in HEK 293 cells expressing Nav1.2, Nav1.3, or Nav1.5. Na + currents in mouse cardiomyocytes and hiPSC-CMs treated with the oxidant chloramine T (ChT) developed a moderate reduction in peak current amplitudes accompanied by large late Na + currents. While ChT induced a strong reduction in peak current amplitudes but only small persistent currents on Nav1.5, both Nav1.2 and Nav1.3 produced increased peak current amplitudes and large persistent currents following oxidation. TTX (300 nM) blocked ChT-induced late Na + currents significantly stronger as compared to peak Na + currents in both mouse cardiomyocytes and hiPSC-CMs. Similar differences between Nav1.2, Nav1.3, and Nav1.5 regarding ROS sensitivity were also evident when oxidation was induced with UVA-light (380 nm) or the cysteine-selective oxidant nitroxyl (HNO). To conclude, our data on TTX-sensitive Na + channels expressed in cardiomyocytes may be relevant for the generation of late Na + currents following oxidative stress.
Keyphrases
- high glucose
- endothelial cells
- diabetic rats
- reactive oxygen species
- heart failure
- photodynamic therapy
- hydrogen peroxide
- machine learning
- nitric oxide
- induced apoptosis
- anti inflammatory
- left ventricular
- big data
- signaling pathway
- newly diagnosed
- ischemia reperfusion injury
- high intensity
- artificial intelligence
- data analysis