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 language||English (US)|
|Number of pages||5|
|Journal||Journal of Biological Chemistry|
|State||Published - May 29 1998|
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