Extracellular potassium and glutamate interact to modulate mitochondria in astrocytes.

Astrocytes clear glutamate and potassium, both of which are released into the extracellular space during neuronal activity. These processes are intimately linked with energy metabolism. Whereas astrocyte glutamate uptake causes cytosolic and mitochondrial acidification, extracellular potassium induces bicarbonate-dependent cellular alkalinization. This study aimed at quantifying the combined impact of glutamate and extracellular potassium on mitochondrial parameters of primary cultured astrocytes. Glutamate in 3mM potassium caused a stronger acidification of mitochondria compared to cytosol. 15mM potassium caused alkalinization that was stronger in the cytosol than in mitochondria. While the combined application of 15mM potassium and glutamate led to a marked cytosolic alkalinization, pH only marginally increased in mitochondria. Thus, potassium and glutamate effects cannot be arithmetically summed, which also applies to their effects on mitochondrial potential and respiration. The data implies that, because of the non-linear interaction between the effects of potassium and glutamate, astrocytic energy metabolism will be differentially regulated.