Human ether-a-go-go-related gene (hERO) potassium (K+) channels carry the rapid delayed rectifier K+ current (IKr) which contributes to the repolarisation of cardiac action potentials. lKr plays a protective role against premature beats and is highly prone to pharmacological inhibition that can lead to acquired Long QT syndrome. Flecainide (a class le antiarrhythmic agent) is used in the treatment of atrial fibrillation; it inhibits IhERg/IKr at clinically relevant concentration and it has been occasionally associated with life-threatening ventricular tachycardia (Torsade de Pointes). Ivabradine is a specific bradycardic agent with a high selectivity for hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels. However, some evidence has raised the possibility that it may affect IKr. The principal aims of this study were to investigate the mechanism of interaction and the molecular determinants of pharmacological block of hERG by flecainide and ivabradine. In an additional set of experiments, the modulation by extracellular potassium ([K+]o) of the response of hERG to premature stimulations was examined.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:688218 |
| Date | January 2015 |
| Creators | Melgari, Dario |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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