Diazoxide and pinacidil uncouple pyruvate-malate-induced mitochondrial respiration

We investigated the effects of K(ATP) channel openers diazoxide and pinacidil on the respiration rate and membrane potential (deltapsi) of rat heart mitochondria, oxidizing pyruvate and malate. Diazoxide and pinacidil (58.8-1348.3 microM) increased the V2 (-ADP) respiration rate accordingly by 13-208% and 30-273% and decreased the deltapsi by 2-17% and 6-55%. These effects were also similar in the respiration medium without K+. Moreover, carboxyatractyloside completely abolished diazoxide- and pinacidil-induced uncoupling, indicating a role for the mitochondrial adenine nucleotide translocase in this process.