A Metabolically Stable Apelin-13 Analog Acting as a Potent ITo Potassium Current Blocker with Potential Benefits for Brugada Syndrome
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Pharmacology study of an apelin-13 analog as a potassium current blocker for Brugada syndrome.
It studies a potential cardiac drug analog for Brugada syndrome, not research practice.
Patch-clamp pharmacology of an apelin analog on cardiac currents; biomedical physiology.
Abstract
Apelin serves as the endogenous ligand for the APJ receptor and enhances cardiac contractility without significantly affecting potassium currents. However, its short in vivo half-life limits clinical application, prompting the development of metabolically stable APJ receptor agonists. This study employed the patch-clamp technique to investigate the effects of the C-terminally modified apelin-13-2Nal derivative (2Nal) on action potential dynamics, rapid sodium (INa), and transient potassium (ITO) currents in rat cardiomyocytes. We discovered that 2Nal prolongs ventricular action potential duration by selectively blocking ITo. Dose-response analysis indicated that 2Nal acts as a partial antagonist of ITO, achieving a maximum blockade of 47%, with an apparent EC50 of 0.3 nM, while not affecting INa. Our lab previously found that an imbalance between ITo and INa currents contributes to the development of cardiac arrhythmias in conditions like Brugada syndrome. Currently, few therapeutic options exist to safely address this imbalance, as sodium channel openers cannot restore it, and most ITo blockers are cardiotoxic. The selective blockade of ITo by 2Nal that we describe here helps restore the balance of electrical currents between ITo and INa. Our study presents a novel, safe partial antagonist of ITo that may help prevent arrhythmias associated with Brugada syndrome.
Stored with the screening record, where it is evidence for the labels above.
The record
- Venue
- International Journal of Molecular Sciences
- Topic
- Apelin-related biomedical research
- Field
- Medicine
- Canadian institutions
- Université de Sherbrooke
- Funders
- Canadian Institutes of Health Research
- Keywords
- PharmacologyAntagonistBrugada syndromePotassium channelCardiac transient outward potassium currentBlockadeChemistryPatch clampApelinMedicineInternal medicineReceptor
- Has abstract in OpenAlex
- yes