H. Ishida et al., Opening of mitochondrial K-ATP channels attenuates the ouabain-induced calcium overload in mitochondria, CIRCUL RES, 89(10), 2001, pp. 856-858
We tested whether opening of mitochondrial ATP-sensitive K+ (mitoK(ATP)) ch
annels depolarizes mitochondrial membrane potential (Delta Psi (m)) and the
reby prevents the mitochondrial Ca2+ overload. With the use of a Nipkow dis
k confocal system, the mitochondrial Ca2+ concentration ([Ca2+](m)) and Del
ta Psi (m) in rat ventricular myocytes were measured by loading cells with
Rhod-2 and JC-1, respectively. Exposure to ouabain (1 mmol/L) for 30 minute
s produced mitochondrial Ca2+ overload, and the intensity of Rhod-2 fluores
cence significantly increased to 173 +/- 16% of baseline (P <0.001). Treatm
ent of myocytes with the mitoK(ATP) channel opener diazoxide (100 mu mol/L)
blunted the ouabain-induced mitochondrial Ca2+ overload (131 +/- 10% of ba
seline; P <0.001 versus ouabain). Moreover, diazoxide significantly depolar
ized the Delta Psi (m). and reduced the intensity of JC-1 fluorescence duri
ng application of ouabain to 89 +/-2% of baseline (P <0.05). These effects
of diazoxide were blocked by the mitoK(ATP) channel blocker 5-hydroxydecano
ate (500 mu mol/L). These results indicate that opening of mitoK(ATP) chann
els prevents a mitochondrial Ca2+ overload in association with Delta Psi (m
). depolarization and thereby protects myocardium against ischernic damage.