| Autor: |
Karpushev AV; Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, 44 Thorez Ave., 194223 Saint Petersburg, Russia.; Almazov National Medical Research Centre, 2 Akkuratova St., 197341 Saint Petersburg, Russia., Mikhailova VB; Almazov National Medical Research Centre, 2 Akkuratova St., 197341 Saint Petersburg, Russia., Klimenko ES; Almazov National Medical Research Centre, 2 Akkuratova St., 197341 Saint Petersburg, Russia., Kulikov AN; Pavlov First State Medical University of St. Petersburg, 6-8 Ulitsa L'va Tolstovo, 197022 Saint Petersburg, Russia., Ivkin DY; Saint Petersburg State Chemical Pharmaceutical University, 14, Prof. Popov Str., 197376 Saint Petersburg, Russia., Kaschina E; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Cardiovascular-Metabolic-Renal (CMR)-Research Center, 10115 Berlin, Germany.; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10115 Berlin, Germany., Okovityi SV; Saint Petersburg State Chemical Pharmaceutical University, 14, Prof. Popov Str., 197376 Saint Petersburg, Russia. |
| Abstrakt: |
Empagliflozin, an inhibitor of sodium-glucose co-transporter 2 (iSGLT2), improves cardiovascular outcomes in patients with and without diabetes and possesses an antiarrhythmic activity. However, the mechanisms of these protective effects have not been fully elucidated. This study aimed to explore the impact of empagliflozin on ion channel activity and electrophysiological characteristics in the ventricular myocardium. The main cardiac ionic currents (I Na , I CaL , I CaT, I Kr , I Ks ) and action potentials (APs) were studied in zebrafish. Whole-cell currents were measured using the patch clamp method in the isolated ventricular cardiomyocytes. The conventional sharp glass microelectrode technique was applied for the recording of APs from the ventricular myocardium of the excised heart. Empagliflozin pretreatment compared to the control group enhanced potassium I Kr step current density in the range of testing potentials from 0 to +30 mV, I Kr tail current density in the range of testing potentials from +10 to +70 mV, and I Ks current density in the range of testing potentials from -10 to +20 mV. Moreover, in the ventricular myocardium, empagliflozin pretreatment shortened AP duration APD as shown by reduced APD50 and APD90. Empagliflozin had no influence on sodium (I Na ) and L- and T-type calcium currents (I CaL and I CaT ) in zebrafish ventricular cardiomyocytes. Thus, we conclude that empagliflozin increases the rapid and slow components of delayed rectifier K + current (I Kr and I Ks ). This mechanism could be favorable for cardiac protection. |
