COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm

Figure 7

Maintaining ATP levels during respiratory viral infection is the key to maintain proper ion distribution to avoid edema. The active and passive cotransporters and channels maintain the ion gradients between AEC and extracellular fluids. The apical ligand-gated channels function to maintain appropriate osmotic pressure to provide sufficient fluid in the airway without causing edema. AEC I express superoxide-activated ENaC Na⁺ channels and NOX2 that regulates them. Abbreviations: 3Na⁺/2K⁺-ATPase: 3 sodium 2 potassium ATPase; AE: anion exchange chloride bicarbonate exchanger; BCFTR: basolateral cystic fibrosis transmembrane conductance regulator-like channel; BHBDH: β-hydroxybutyrate dehydrogenase; BIRC: basolateral inward rectifying channel; BK_Ca: large-conductance Ca²⁺- and voltage-gated big K⁺ channel; BORC: basolateral outward rectifying channel; CACC/TMEM: calcium-activated chloride channels/transmembrane protein; CFTR: cystic fibrosis transmembrane conductance regulator; CNG: cyclic nucleotide-gated ion channel; ENaC: epithelial sodium channel; KCa3.1: calcium-activated potassium channel; Kv7.1: voltage-dependent potassium channel; NCX: sodium calcium exchanger; NHE: sodium-hydrogen exchanger; NKCC: sodium potassium chloride cotransporter; NOX2: NADPH oxidase 2; Pit1/2: sodium-dependent phosphate transporters 1 and 2; RYR: ryanodine receptor calcium-induced Ca²⁺ channel; SERCA: sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase; SK4: SK4 calcium-activated potassium channel.