Abstract
The effect of pinacidil was studied on calcium-loaded rat heart mitochondria (RHM) in the presence of succinate and rotenone. In experiments with pinacidil, the swelling of these mitochondria increased in media with NH4NO3 or K-acetate, but the inner membrane potential (ΔΨmito) and the respiration in 3 or 2,4-dinitrophenol-stimulated states of these organelles decreased due to the opening of the mitochondrial permeability transition pore (MPTP) in their inner membrane. These effects were inhibited by cyclosporin A and ADP. It was concluded that the protective effect of pinacidil in the cardiac muscle under ischemia/reperfusion may be associated with both the stimulation of mitochondrial swelling and a decrease in RHM calcium overload resulted in ΔΨmito fall due to mild uncoupling effect of pinacidil.
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ACKNOWLEDGMENTS
We are grateful to S.A. Konovalova for her assistance in measuring the safranin fluorescence in the experiments with the isolated rat heart mitochondria. Safranin fluorescence was measured using of Research Resource Center equipment for the physiological, biochemical and molecular biological studies (Sechenov Institute of Evolutionary physiology and Biochemistry, the Russian Academy of Sciences).
Funding
The study was performed in the framework of the State Assignment of the Federal Agency for Scientific Organizations (FASO) of the Russian Federation (theme no. AAAA A18-118012290142-9).
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Translated by M. Batrukova
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Korotkov, S.M., Brailovskaya, I.V., Nesterov, V.P. et al. Effects of Pinacidil and Calcium on Succinate-Energized Rat Heart Mitochondria in the Presence of Rotenone. Dokl Biochem Biophys 487, 277–281 (2019). https://doi.org/10.1134/S1607672919040070
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DOI: https://doi.org/10.1134/S1607672919040070