Cytokine Effects on Mechano-Induced Electrical Activity in Atrial Myocardium

• Published in: Immunological investigations 2017-01, Vol.46 (1), p.22-37
• Main Authors: Kazanski, V., Mitrokhin, V. M., Mladenov, M. I., Kamkin, A. G.
• Format: Article
• Language: English
• Subjects: Action Potentials - immunology; Animals; Atrial Function - immunology; Atrial myocardium; cytokines; Cytokines - immunology; Cytokines - metabolism; Electric Conductivity; Electricity; Heart Atria - pathology; Humans; mechanical stretch; Mechanotransduction, Cellular - immunology; Myocardial Contraction; Myocardium - immunology; Myocardium - metabolism; Rats; Signal Transduction; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0882-0139; 1532-4311
• DOI: 10.1080/08820139.2016.1208220

The role of cytokines as regulators of stretch-related mechanisms is of special importance since mechano-sensitivity plays an important role in a wide variety of biological processes. Here, we elucidate the influence of cytokine application on mechano-sensitivity and mechano-transduction. The atrial myocardial stretch induces production of interleukin (IL)-2, IL-6, IL-13, IL-17A, and IL-18 with exception of tumor necrosis factor α (TNF-α), IL-1β, and vascular endothelial growth factor B (VEGF-B). Positive ionotropic effect was specific for VEGF-B, negative ionotropic effects were specific for TNF-α, IL-1β, IL-2, IL-6, IL-13, IL-17A and IL-18, while IL-1α doesn't show direct ionotropic effect. The IL-2, IL-6, IL-17A, IL-18, and VEGF-B cause elongation of the APD, in comparison with the reduced APD caused by the IL-13. The TNF-α, IL-1β, and IL-18 influences L-type Ca 2+ channels, IL-2 has an inhibitory effect on the fast Na + channels while IL-17A and VEGF-B were specific for Kir channels. With exception of the IL-1α, IL-2, and VEGF-B, all analyzed cytokines include nitric oxide dependent signaling with resultant combined effects on mechano-gated and Ca 2+ channels. The relationships between these pathways and the time-dependence of their activation are of important considerations in the evaluation of cytokine-induced electrical abnormality, specific for cardiac dysfunctions. In general, the discussion presented in this review covers research devoted to counterbalance between different cytokines in the regulation of stretch-induced effects in rat atrial myocardium. Abbreviations: APs: action potentials; APD25: action potential durations to 25% of re-polarization; APD50: action potential durations to 50% of repolarization; APD90: action potential durations to 90% of repolarization; MGCs: mechanically gated channels