P938Regulation of the delayed rectifier potassium current during the adrenergic adaptation of cardiomyocytes
| Autor: | B Kurtan, Péter P. Nánási, C S Dienes, Tamás Bányász, Z S Kovacs, D Baranyai, Norbert Szentandrássy, D Kiss, Roland Veress, Balázs Horváth, T Hezso, János Magyar |
|---|---|
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | EP Europace. 22 |
| ISSN: | 1532-2092 1099-5129 |
| DOI: | 10.1093/europace/euaa162.191 |
| Popis: | Funding Acknowledgements Supported by the ÚNKP-19-3 New National Excellence program of the Ministry for Innovation and Technology Introduction and aims Adaptation of the human heart to physical activity is a complex mechanism that includes the change of heart rate, morphology of the action potential (AP) among others. Stimulation of β-adrenergic receptors (β-AR) causes the shortening of the AP duration of ventricular cardiomyocytes. This is caused by the regulation of the potassium currents by the β-adrenergic signaling pathway. Our aim was to investigate the role of protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII) in the regulation of the slow component (IKs) of the delayed rectifier potassium current under β-AR activation. Methods Our experiments were performed on isolated canine cardiomyocytes from the left ventricle. The IKs current profile was determined under a ventricular AP. We used "AP voltage clamp" conditions in six experimental groups: Control (CTRL), β-AR stimulation with isoproterenol (ISO), CaMKII inhibition with KN-93 (KN-93), PKA inhibition with H-89 (H-89) β-AR stimulation with inhibited CaMKII (KN-93 + ISO), β-AR stimulation with inhibited PKA (H-89 + ISO). β-AR stimulation with inhibited CaMKII and PKA (KN-93 + H-89 + ISO) Results The highest current density of IKs was approximately 6 times higher and the charge delivered by IKs was about 8 times larger in the ISO group than in CTRL or KN-93 conditions. In the KN-93 + ISO group, IKs amplitude was about 60% smaller and delivered about half the total charge compared to the ISO group. In the H‑89 + ISO group, IKs was about 30% smaller and delivered 40% less total charge than in the ISO group. In the KN-93 + H-89 + ISO group the IKs did not changed sicnificantly. Conclusion Based on our results, CaMKII plays an important role in regulating IKs by β-AR stimulation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|