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Cardiomyocytes' prolonged IL‐2 incubation induces enhancement in L‐type Ca 2+ channels mediated by inhibitory‐kappaB kinase/nuclear factor‐kappaB signalling
Author(s) -
Mitrokhin Vadim,
Gorbacheva Lyubov,
Vachrushev Nikita,
HadziPetrushev Nikola,
Kamkin Andre,
Mladenov Mitko
Publication year - 2021
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13491
Subject(s) - incubation , nitric oxide synthase , kinase , nitric oxide , intracellular , microbiology and biotechnology , inhibitory postsynaptic potential , chemistry , biology , medicine , endocrinology , biochemistry
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 I Ca,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 I Ca,L . IL‐2 (3 ng/mL) induced a significant increase in phosphorylated NF‐κB p65. The cardiomyocytes incubated in a Kraftbrühe solution containing IL‐2 plus PDTC as a specific inhibitor of inducible nitric oxide synthase (iNOS) for 2 hours had a similar I Ca,L increase compared to the cells incubated only in IL‐2. IL‐2‐induced enhancement in L‐type Ca 2+ channels was mediated by IKK/NF‐κB signalling, but not via iNOS‐mRNA signalling.