Effect of diazoxide on the mitochondrial respiration of skeletal muscle

Abstract

Mitochondrial KATP channels were described by Inoue (1991) by patch clamp techniques on isolated mitochondria of liver. Later on were described on mitochondria of heart and brain. Potassium channels are inhibited by sulfonylurea and activated by potassium channel openers (KCOs). It has been reported that diazoxide is a potent selective opener of the mitochondrial KATP channel (Garlid et al., 1997; Sato et al., 1998) in a range of 10 to 50 μM (Kowaltowski et al., 2001). Also, it has been proposed that this drug can act on other proteins of the respiratory chain, like succinate dehydrogenase enzyme, with concentrations up the 100 μM (Hanley et al., 2002). In the present work we investigated the effect of diazoxide (100 – 500 μM) on mitochondrial respiration of skeletal muscle of chick, using different substrates. We observed a dose‐dependent inhibition using glutamate‐malate and succinate as substrates for complex I and II, respectively (40% of inhibition). The dose used is higher of those reported for cardiac and skeletal muscle, reason why we conclude that mito‐KATP of skeletal muscle is less sensitive to KCOs and we do not discard that the effect could be do to the effect on the membrane potential or calcium uptake. It is required a more complete analysis to contribute a concrete conclusion. Supported by the grants from FRABA to X.T., COECYT, Fondos Mixtos Gob. Michoacán‐CONACYT (64277) and CIC‐UMSNH (2.16) to S‐M.A.