Arrhythmogenic and antiarrhythmic actions of late sustained sodium current in the adult human heart
| Autor: | Eduardo Hernandez, Christina Mai, Tim Indersmitten, Lana Rasoul, Andrew Macias, Valentyna Geft, Najah Abi-Gerges, Katrina Sweat, Paul E. Miller, Alexa Stafford, Andrea Ghetti, William Nguyen, Tamara Cotta, Tiara Wong, Ky Truong, Anh Tuan Ton, Ana Espinoza, Guy Page, Yannick Miron |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult ERG1 Potassium Channel Pyridines Science hERG Cardiology Ranolazine 030204 cardiovascular system & hematology Pharmacology Article Sodium current Membrane Potentials Contractility 03 medical and health sciences 0302 clinical medicine Cnidarian Venoms Piperidines Atrial Fibrillation Medicine Humans Myocytes Cardiac cardiovascular diseases Heart Atria Multidisciplinary biology business.industry Sodium Models Cardiovascular Human heart Long-term potentiation Atrial fibrillation Triazoles medicine.disease 030104 developmental biology biology.protein Calcium business Homeostasis medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-16 (2021) |
| ISSN: | 2045-2322 |
| Popis: | Late sodium current (late INa) inhibition has been proposed to suppress the incidence of arrhythmias generated by pathological states or induced by drugs. However, the role of late INa in the human heart is still poorly understood. We therefore investigated the role of this conductance in arrhythmias using adult primary cardiomyocytes and tissues from donor hearts. Potentiation of late INa with ATX-II (anemonia sulcata toxin II) and E-4031 (selective blocker of the hERG channel) slowed the kinetics of action potential repolarization, impaired Ca2+ homeostasis, increased contractility, and increased the manifestation of arrhythmia markers. These effects could be reversed by late INa inhibitors, ranolazine and GS-967. We also report that atrial tissues from donor hearts affected by atrial fibrillation exhibit arrhythmia markers in the absence of drug treatment and inhibition of late INa with GS-967 leads to a significant reduction in arrhythmic behaviour. These findings reveal a critical role for the late INa in cardiac arrhythmias and suggest that inhibition of this conductance could provide an effective therapeutic strategy. Finally, this study highlights the utility of human ex-vivo heart models for advancing cardiac translational sciences. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink