FIGURE 11.

Illustration of the effect of NBCe1-B/C absence on the integrated physiologic response to MAc. Induction of MAc by NH₄Cl stimulates central chemoreceptors that trigger the secondary respiratory response. The resulting increase in ventilation lowers pCO₂, which helps mitigate the primary fall in plasma pH. Concurrently, MAc stimulates renal ammoniagenesis in attempt to increase HCO₃ ⁻ production to replace the HCO₃ ⁻ consumed in buffering the acid-load. In the absence of NBCe1-B/C, as demonstrated by KO_b/c mice, the secondary respiratory response to MAc is impaired. Therefore, there is no change in pCO₂ during MAc, which leads to an initial greater severity of acidemia. However, NBCe1-A expression in the kidney remains intact, specifically in proximal tubules (PTs) located in the cortical labyrinth. Therefore, the greater severity of acidemia in KO_b/c mice prompts an enhancement of ammoniagenesis in NBCe1-A expressing PTs that ultimately recovers plasma pH equal to that of wild-type mice. This enhancement of ammoniagenesis appears to overshadow any potential defect in ammoniagenesis resulting from NBCe1-B loss (NBCe1-B being usually expressed in PTs of the outer segment of the outer medulla (OSOM)).