State-dependent inhibition of the mitochondrial K(ATP) channel by glyburide and 5-hydroxydecanoate

Martin Jabůrek, Vladimir Yarov-Yarovoy, Petr Paucek, Keith D. Garlid

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Abstract

The mitochondrial K(ATP) channel (mitoK(ATP)) is hypothesized to be the receptor for the cardioprotective effects of K+ channel openers (KCO) and for the blocking of cardioprotection by glyburide and 5-hydroxydecanoate (5- HD). Studies on glyburide have indicated that this drug is inactive in isolated mitochondria. No studies of the effects of 5-HD on isolated mitochondria have been reported. This paper examines the effects of glyburide and 5-HD on K+ flux in isolated, respiring mitochondria. We show that mitoK(ATP) is completely insensitive to glyburide and 5-HD under the experimental conditions in which the open state of the channel is induced by the absence of ATP and Mg2+. On the other hand, mitoK(ATP) became highly sensitive to glyburide and 5-HD when the open state was induced by Mg2+, ATP, and a physiological opener, such as GTP, or a pharmacological opener, such as diazoxide. In these open states, glyburide (K 1/4 values 1-6 μM) and 5-HD (K 1/4 values 45-75 μM) inhibited specific, mitoK(ATP)-mediated K+ flux in both heart and liver mitochondria from rat. These results are consistent with a role for mitoK(ATP) in cardioprotection and show that different open states of mitoK(ATP), although catalyzing identical K+ fluxes, exhibit very different susceptibilities to channel inhibitors.

Original languageEnglish (US)
Pages (from-to)13578-13582
Number of pages5
JournalJournal of Biological Chemistry
Volume273
Issue number22
StatePublished - May 29 1998
Externally publishedYes

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Glyburide
Mitochondria
Fluxes
Adenosine Triphosphate
Diazoxide
Heart Mitochondria
Liver Mitochondrion
Guanosine Triphosphate
Liver
mitochondrial K(ATP) channel
5-hydroxydecanoic acid
Rats
Pharmacology
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry

Cite this

State-dependent inhibition of the mitochondrial K(ATP) channel by glyburide and 5-hydroxydecanoate. / Jabůrek, Martin; Yarov-Yarovoy, Vladimir; Paucek, Petr; Garlid, Keith D.

In: Journal of Biological Chemistry, Vol. 273, No. 22, 29.05.1998, p. 13578-13582.

Research output: Contribution to journalArticle

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