Intramitochondrial pH and ammonium production in rat and dog kidney cortex

The focus of this investigation was to compare data from isolated tubules and mitochondria of rat and dog kidneys subjected to altered medium pH (pHe) in vitro and to determine the effects of pH on ammonium production. Cytosolic pH (pHi) was determined using the fluoroprobe BCECF-AM; mitochondrial matrix pH (pHm) was estimated from the distribution of a labeled weak acid. The data indicate differences between rat and dog. pHi was consistently lower in rat than dog proximal tubules. In rat, pHm decreased in parallel with pHe and phi, accounting, at least in part, for the accelerated alpha-ketoglutarate dehydrogenase (alpha KGDH) flux, which is important in triggering increased ammoniagenesis. In dog, pHm varied to only a small extent with pHe and pHi changes. The results suggest that changes in pHm are unlikely to explain an increase in alpha KGDH flux in acute acidosis in the dog. However, pHe and pHi could conceivably lead to alterations in other factors than pHm, i.e. matrix Ca2+, which may facilitate accelerated ammonium production.