Large-Conductance Potassium Cation Channel Opener NS1619 Inhibits Cardiac Mitochondria Respiratory Chain

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Abstract
It has recently been reported that large-conductance calcium-cation-activated potassium channels, also known as BK(Ca)-type potassium channels, are present in the inner membranes of cardiac cell mitochondria. It was also shown that the BK(Ca)-channel opener NS1619 (1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one) protects the heart against ischemic damage. In the present study we investigated the effects of NS1619 on the function of isolated cardiac mitochondria. In particular, we examined the influence of NS1619 on mitochondrial membrane potential and mitochondrial respiration. We showed that NS1619 decreases the mitochondrial membrane potential and inhibits the mitochondrial respiratory chain. Our results demonstrate that the protection induced by this channel opener in the heart may also be caused by pharmacological preconditioning through the inhibition of the mitochondrial respiratory chain.