Fig. 1

Biological effects of pH on microglia, cardiomyocytes, and lung epithelial cells. Microglia expresses two classes of acid-base transporting proteins: acid loaders (red) and acid extruders (blue). In acidosis, acid extruder proteins are increased while in alkalosis these are downregulated. In cardiomyocytes, the regulation of the adrenergic receptors is determined by β-arrestins, which can trigger the internalization process of dephosphorization or degradation and therefore define the up- and downregulation of the internalized molecule either to recycling or degradation, respectively. In acidosis, adrenergic receptors are downregulated and less responsive to catecholamines. In the lung epithelium, reduction of lung edema clearance is associated with the endocytosis of the Na+/K+-ATPase from the plasma membrane of alveolar epithelial cells, which leads to decreased Na+/K+-ATPase activity. During acidosis, protein kinase C (PKC)-ζ phosphorylates the Na+/K+-ATPase α1-subunit, leading to endocytosis of the Na+/K+-ATPase. The activation of PKC-ζ is regulated by AMP kinase (AMPK). Acidosis culminates in the Na+/K+-ATPase endocytosis from the cell plasma membrane. In the lung epithelium, alkalosis with low carbon dioxide and hyperventilation can determine increase of mechanical power and activation of the inflammatory system