Recombinant Rat CA4 contributes to extracellular buffering in the hippocampus by modulating alkaline transients during neuronal activity. Knockout (KO) mouse models revealed:
CA4 and CA XIV redundantly regulate interstitial pH, with CA4 accounting for ~60% of buffering capacity .
Double KO mice (CA4/CA14) exhibit amplified alkaline shifts (2-fold increase vs. WT), confirming synergistic roles .
Anchored to luminal surfaces of renal tubules and pulmonary capillaries via GPI linkage, CA4 facilitates bicarbonate transport and CO₂ excretion .
In renal proximal tubules, it enhances AE3-mediated Cl⁻/HCO₃⁻ exchange, critical for maintaining acid-base balance .
Retinitis Pigmentosa (RP17): Mutations in CA4 disrupt retinal pH homeostasis, leading to photoreceptor degeneration .
Metabolic Acidosis: Impaired CA4 activity correlates with bicarbonate transport defects in renal tubules .
Current limitations include the lack of full-length protein constructs in commercial preparations . Future studies could explore: