Interactions between intracellular chloride concentrations, intracellular pH and energetic status in rat lactotrope cells in primary culture

Rat lactotrope cells in primary cultures have a higher intracellular Cl- concentration ([Cl-]i) than that predicted by a passive distribution across the membrane. This suggests that active cellular mechanisms ensure this ionic equilibrium. In this study, we examined the interactions between pHi, [Cl-]i regulation and cell energetics. We analyzed: 1. the interactions between extracellular Cl- concentrations, [Cl-]i and cellular energy; 2. the influence of [Cl-]i on respiratory chain function; 3. the correlation with glycolysis and; 4. the role played by pHi in these cellular mechanisms. We show that low [Cl-]i decreases ATP cell content, ATP/ADP ratio and modify phosphorylative oxidations. ATP production is rather due to the anaerobic pathway of the glucose metabolism than the aerobic one and depends also on other metabolic substrates among which glutamine probably has a special role. Finally, pHi appears as a determinant in the balance between aerobic and anaerobic pathways. These results are discussed in relation to the role of Cl- in normal and pathological (effect of hypoxia on mature and immature neurons) cell situations.