Gramicidin and Ion Transport in Isolated Liver Mitochondria.

1. Gramicidin caused H(+) production by liver mitochondria; this process was dependent on the presence of Na(+), Li(+), Rb(+) or Cs(+). In the presence of one of these alkali-metal ions and phosphate, gramicidin caused mitochondrial swelling and increased oxygen consumption. 2. Uncoupling agents, anaerobic conditions or respiratory inhibitors both inhibited and reversed H(+) production and swelling. Both these processes could be supported by coupled electron transport through even a restricted portion of the respiratory chain. 3. NH(4) (+) also caused stimulation of respiration in the presence of gramicidin. In this case phosphate was not required. NH(4) (+), in the presence of gramicidin, caused contraction of the mitochondria and a reversal of K(+)-induced swelling and H(+) production. 4. Uncoupling agents or NH(4) (+) together with gramicidin caused the release of Sr(2+) that had been accumulated by mitochondria in the presence of phosphate. 5. These results are discussed in relation to a postulated respiration-dependent H(+) pump located in the mitochondrial membrane. It is suggested that gramicidin allows alkali-metal ions to pass through the mitochondrial membrane.