Effect of CO2 Concentration on Intracellular pH and on Glycogen Synthesis from Glycerol and Glucose in Isolated Perfused Rat Liver

Abstract

The effect of variation of extracellular total CO2 concentration at constant pH on intracellular pH and total intracellular CO2 content and on the conversion of glycerol-1,3-14C and glucose uniformly labeled with 14C to glycogen in perfused rat liver has been studied. The concentration of perfusate CO2 was varied from 8 to 40 m m while pH was maintained between 7.4 and 7.5. At the end of a 60-min perfusion period with perfusate of either CO2 concentration, the intracellular pH remained constant in the range of pH 7.0 to 7.1. Intracellular total CO2 content followed the changes in extracellular total CO2 content but was generally 25% lower than the extracellular concentration. Under similar perfusion conditions, liver glycogen content was increased 30 to 60% and glycerol-1,3-14C conversion to glycogen by 90 to 100% by perfusion with an average total CO2 concentration of 33 m m as compared to 9 m m total CO2 in the presence of 13 m m glycerol and 15 m m glucose as substrate. When the only added substrate was glucose adjusted to 5.6 m m initially, glycogen content was not markedly altered by the CO2 content of the perfusate, but the conversion of glucose uniformly labeled with 14C to glycogen was increased 90% over control values when the liver was perfused the 1st hour with perfusate containing 11 m m CO2 followed by perfusion the 2nd hour with 34 m m CO2. These results suggest that variation in extracellular total CO2 concentration within physiological limits does produce alterations in glycogen metabolism by variation of total intracellular CO2 concentration and not by variation in the average intracellular pH. The results suggest that total intracellular CO2 concentration may be an important physiological regulator of carbohydrate metabolism.