Heme is required for carbon monoxide activation of mitochondrial BK Ca channel.

Autor: Rotko D; Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pastuera 3, 02-093, Warsaw, Poland., Bednarczyk P; Department of Physics and Biophysics, Institute of Biology, Warsaw University of Life Sciences-SGGW, Nowoursynowska 159, 02-776, Warsaw, Poland., Koprowski P; Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pastuera 3, 02-093, Warsaw, Poland., Kunz WS; Division of Neurochemistry, Department of Experimental Epileptology and Cognition Research University of Bonn, Sigmund-Freud Strasse 25, 53105, Bonn, Germany., Szewczyk A; Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pastuera 3, 02-093, Warsaw, Poland., Kulawiak B; Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pastuera 3, 02-093, Warsaw, Poland. Electronic address: b.kulawiak@nencki.edu.pl.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2020 Aug 15; Vol. 881, pp. 173191. Date of Electronic Publication: 2020 May 15.
DOI: 10.1016/j.ejphar.2020.173191
Abstrakt: Carbon monoxide (CO) is an endogenously synthesized gaseous mediator and is involved in the regulation of numerous physiological processes. Mitochondria, in which hemoproteins are abundant, are among the targets for CO action. Large-conductance calcium-activated (mitoBK Ca ) channels in the inner mitochondrial membrane share multiple biophysical similarities with the BK Ca channels of the plasma membrane and could be a potential target for CO. To test this hypothesis, the activity of the mitoBK Ca channels in human astrocytoma U-87 MG cell mitochondria was assessed with the patch-clamp technique. The effects of CO-releasing molecules (CORMs), such as CORM-2, CORM-401, and CORM-A1, were compared to the application of a CO-saturated solution to the mitoBK Ca channels in membrane patches. The applied CORMs showed pleiotropic effects including channel inhibition, while the CO-containing solution did not significantly modulate channel activity. Interestingly, CO applied to the mitoBK Ca channels, which were inhibited by exogenously added heme, stimulated the channel. To summarize, our findings indicate a requirement of heme binding to the mitoBK Ca channel for channel modulation by CO and suggest that CORMs might have complex unspecific effects on mitoBK Ca channels.
(Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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