The investigation of the cellular electrophysiological and antiarrhythmic effects of a novel selective sodium–calcium exchanger inhibitor, GYKB-6635, in canine and guinea-pig hearts
| Autor: | Zoltán Márton, Károly Acsai, Claudia Corici, Norbert Jost, Zsófia Kohajda, Amir Geramipour, Kinga Oravecz, András Tóth, Norbert Nagy, László Virág, András Varró, Zsolt Szakonyi, János Prorok |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pharmacology Sodium-calcium exchanger Physiology Chemistry chemistry.chemical_element Depolarization General Medicine 030204 cardiovascular system & hematology Membrane transport Calcium Guinea pig 03 medical and health sciences Electrophysiology 030104 developmental biology 0302 clinical medicine Physiology (medical) Patch clamp Homeostasis |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 94:1090-1101 |
| ISSN: | 1205-7541 0008-4212 |
| Popis: | The sodium–calcium exchanger (NCX) is considered as the major transmembrane transport mechanism that controls Ca2+ homeostasis. Its contribution to the cardiac repolarization has not yet been directly studied due to lack of specific inhibitors, so that an urgent need for more selective compounds. In this study, the electrophysiological effects of GYKB-6635, a novel NCX inhibitor, on the NCX, L-type calcium, and main repolarizing potassium currents as well as action potential (AP) parameters were investigated. Ion currents and AP recordings were investigated by applying the whole-cell patch clamp and standard microelectrode techniques in canine heart at 37 °C. Effects of GYKB-6635 were studied in ouabain-induced arrhythmias in isolated guinea-pig hearts. At a concentration of 1 μmol/L, GYKB significantly reduced both the inward and outward NCX currents (57% and 58%, respectively). Even at a high concentration (10 μmol/L), GYKB-6635 did not change the ICaL, the maximum rate of depolarization (dV/dtmax), the main repolarizing K+ currents, and the main AP parameters. GYKB-6635 pre-treatment significantly delayed the time to the development of ventricular fibrillation (by about 18%). It is concluded that GYKB-6635 is a potent and highly selective inhibitor of the cardiac NCX and, in addition, it is suggested to also contribute to the prevention of DAD-based arrhythmias. |
| Databáze: | OpenAIRE |
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