Lactate supply as a determinant of the distribution of intracellular pH within the hepatic lobule

When isolated livers from starved rats are perfused with lactate at constant perfusate pH and Pco2, there is a marked gradient of cell pH (pHi) along the length of the lobular radius, with periportal cells being substantially more alkaline than perivenous cells. In the present studies, the perivenous 21% of the lobular volume was destroyed by retrograde digitonin perfusion, and antegrade perfusion restored. pHi was determined by 31P-NMR. The remaining periportal cells, the site of gluconeogenesis from lactate, had a substantially higher mean pHi (7.42) than did the intact liver (7.23). When lactate was removed from the perfusate, mean pHi decreased to 7.25. The corresponding concentration of cell bicarbonate fell with a half-time of approximately 5min. When lactate was re-introduced mean pHi rose to 7.34. We conclude that a major contributor to periportal alkalinity under these conditions is proton consumption during gluconeogenesis from lactate ions.