S.N Pyvovar, V.I. Korzhov., R.B Strutinskii, L.M. Yagupolskii, A.A. Moibenko
S.N Pyvovar, V.I. Korzhov., R.B Strutinskii, L.M. Yagupolskii, A.A. Moibenko
O. O. Bogomolets Institute of Physiology, National Academyof Sciences of Ukraine, Kyiv
Abstract
The cardioprotective mechanism of KATP channel openers
and especially their influence on mitochondrial respiration
has not been clarified yet. In this article we investigated
the effect of DiazoFm and DiazoFp, the new fluor-
containing analogues of diazoxide and the potential
mitochondrial KATP channel openers, on the oxidative
phosphorylation in the isolated mitochondria. It was
shown that the influence of KATP channel openers on ADP-
stimulated oxygen consumption (State 3) depended on the
substrates we used (succinate or 2-oxoglutarate sodium). We
С.М. Пивовар, В.І. Коржов, Р.Б. Струтинський, Л.М. Ягупольський, О.О. Мойбенко
23ISSN 0201-8489 Фізіол. журн., 2006, Т. 52, № 3
have shown that the depression of State 3 was less when we
used DiazoFm (30 мM) and DiazoFp (30 мM) in comparison
with Diazoxide in experiments where succinate was used. The
fluor-containing KATP channels openers did not significantly
change the activity of succinate dehydrogenase in comparison
with diazoxide (it decreased succinate dehydrogenase activity
by 27%). Thus, the fluor-containing analogues of diazoxide
did not significant influence on the complex II of the respiratory
chain. In the other experiments when we used 2-oxoglutarate
sodium as an oxidative substrate, DiazoFp increased ADP-
stimulated oxygen consumption by 33%. All the studied KATP
openers have an uncoupling effect, regardless the substrates
we used. This effect was more significant when we used
succinate as a substrate. We have shown that the uncoupling
effect of oxidative phosphorylation is a consequence of KATP
channels activation. This statement was proved by
5-hydroxydecanoate (200 мM) with depressed influence of
Diazoxide and its fluoring-containing analogues.
Conclusion. The fluor-containig KATP channels openers had not
direct influence on the respiratory chain in mitochondria, but
activation mitochondrial KATP channels by them lead to
uncoupling phosporylation and respiration
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