Cytokine Effects on Mechano-Induced Electrical Activity in Atrial Myocardium.
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 Ca2+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 Ca2+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.


BACKGROUND
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.
a Department of Fundamental and Applied Physiology , Russian National Research Medical University , Moscow , Russia.
V
V
Kazanski
a Department of Fundamental and Applied Physiology , Russian National Research Medical University , Moscow , Russia.
V M
VM
Mitrokhin
a Department of Fundamental and Applied Physiology , Russian National Research Medical University , Moscow , Russia.|b Faculty of Natural Sciences and Mathematics, Institute of Biology , "Ss. Cyril and Methodius" University , Skopje , Macedonia.
M I
MI
Mladenov
a Department of Fundamental and Applied Physiology , Russian National Research Medical University , Moscow , Russia.
A G
AG
Kamkin
D000200:Action Potentials / Q000276:immunology; D000818:Animals; D016275:Atrial Function / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism*; D004553:Electric Conductivity; D004560:Electricity; D006325:Heart Atria / Q000473:pathology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000276:immunology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A
Atrial myocardium; cytokines; mechanical stretch