Control of MCT1 function in cerebrovascular endothelial cells by intracellular pH

Monocarboxylic Acid Transporter 1 (MCT1) is expressed on the plasma membrane of cerebrovascular endothelial cells where it is the only known facilitator of lactic acid transport across the blood brain barrier. During stroke, brain injury, and certain other brain pathologies, anaerobic glycolysis produces severe lactic acidosis of brain tissue leading to brain cell damage. Therefore, a better understanding of factors that control MCT1 function may be the key to better understanding the origins and treatment of pathological lactic acidosis. In this study, we characterized the effects of intracellular pH in controlling MCT1 function and showed that microtubule disruption targeted this mechanism in rat cerebrovascular endothelial cells. Acidic intracellular pH values were shown to strongly inhibit lactic acid transport into the cytoplasmic space, while alkalinization of the cytoplasm significantly enhanced this transport function. These results support a better understanding of how cerebrovascular endothelial MCT1 may contribute to the development of lactic acidosis in brain pathologies, and suggest targeting it as a novel therapy.

Research highlights
► Intracellular pH controls MCT1 function in RBE4 cells.
► Acidic intracellular pH blocks MCT1 function in RBE4 cells.
► Alkaline intracellular pH increases MCT1 function in RBE4 cells.
► Cytoskeletal disruption controls intracellular pH and MCT1 in RBE4 cells.
► Brain endothelial intracellular pH could be targeted as a therapy for stroke.