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International Journal of Physiology and Pathophysiology
SJR: 0.116

ISSN Imprimer: 2155-014X
ISSN En ligne: 2155-0158

Archives: Volume 1, 2010 to Volume 9, 2018

International Journal of Physiology and Pathophysiology

DOI: 10.1615/IntJPhysPathophys.v5.i4.60
pages 333-343

New Fluorine-Containing Openers of ATP-sensitive Potassium Channels Flocalin and Tioflocalin Inhibit Calcium-Induced Mitochondrial Pore Opening in Rat Hearts

Nataliya A. Strutynska
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Ruslan B. Strutynskyi
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Snizhana V. Chorna
Bogomoletz Institute of Physiology, National Academy of Science of Ukraine, Kyiv
Olena M. Semenykhina
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Lidiya A. Mys
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Oleksiy O. Moibenko
International Center for Astronomical and Medico-Biological Research, National academy of Sciences of Ukraine, Department of Experimental Cardiology, Department of General and Molecular Pathophysiology, Bogomoletz institute of Physiology, Kyiv, Ukraine
Vadim F. Sagach
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine

RÉSUMÉ

In vitro experiments on the mitochondria isolated from the rat's heart, we studied the effects of flocalin and tioflocalin, the openers of ATP-sensitive potassium channels (KATP-channels), on the calcium-induced mitochondrial permeability transition pore (MPTP) opening. Both flocalin and tioflocalin caused moderate calcium-independent mitochondria swelling, typical of an activation of KATP-channels, which was prevented by 5-hydroxydecanoate (5-HD), a specific inhibitor of the latter. It allowed us to attribute those compounds to pharmacological openers of just mitochondrial KATP-channels. The concentration-dependent effects of both flocalin and tioflocalin (10−7 to 10−4 M) on Ca2+-induced mitochondrial swelling (MPTP opening) in the heart have been shown, with IC50 = 50 µM and IC50 = 2.7 µM, respectively, and more powerful cardioprotective action of the latter. Administration of those compounds in vivo experiments decreased the sensitivity of the MPTP opening to Ca2+. In particular, flocalin (10−5, 510−5, and 10−4 M) prevented Ca2+-induced MPTP opening by 23.9%, 50.5%, and 100%, while tioflocalin (10−6, 510−6 i 10−5 M) - by 20.2%, 69% and 100%, respectively. Thus, under physiological conditions, the openers of KATP-channels are likely to exert the membrane-stabilizing effects, thereby effectively increasing organelle resistance to Ca2+, the MPTP inductor. The results obtained testify that KATP-channels have importance as cardioprotectors and regulators of MPTP formation in the heart, and they exert anti-ischemic and anti-apoptotic effects, which can be used in correction of mitochondrial dysfunction under pathological conditions of the cardiovascular system.


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