Cardiomyocytes' prolonged IL‐2 incubation induces enhancement in L‐type Ca 2+ channels mediated by inhibitory‐kappaB kinase/nuclear factor‐kappaB signalling

Autor: Mitko Mladenov, Andre Kamkin, L. R. Gorbacheva, Nikola Hadzi-Petrushev, V.M. Mitrokhin, Nikita Vachrushev
Rok vydání: 2020
Předmět:
Zdroj: Basic & Clinical Pharmacology & Toxicology. 128:234-240
ISSN: 1742-7843
1742-7835
Popis: The main objective of this study was to determine the primary intracellular signalling pathway affected by prolonged (2 hours) incubation in interleukin-2 (IL-2). Based on the inflammatory nature of IL-2, priority was given to the involvement of inhibitory-kappaB kinase/nuclear factor-kappaB (IKK/NF-κB) signalling. All of the experiments were performed on freshly prepared cardiomyocytes isolated from rat left ventricles. After isolation, the whole-cell voltage-clamp recordings were performed on single cells. After 2 hours of incubation in IL-2, the current at 0 mV was approximately 100% higher than at the start of the incubation. ACHP, a highly specific kinase β inhibitor, in a concentration of 10 nmol/L, caused significant reduction in the ICa,L . IL-2 (2 ng/mL) in the presence of 0.1 μmol/L IMD-0354 as a specific inhibitor of IKKβ, caused nearly no changes in the ICa,L . IL-2 (3 ng/mL) induced a significant increase in phosphorylated NF-κB p65. The cardiomyocytes incubated in a Kraftbruhe solution containing IL-2 plus PDTC as a specific inhibitor of inducible nitric oxide synthase (iNOS) for 2 hours had a similar ICa,L increase compared to the cells incubated only in IL-2. IL-2-induced enhancement in L-type Ca2+ channels was mediated by IKK/NF-κB signalling, but not via iNOS-mRNA signalling.
Databáze: OpenAIRE
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