A mathematical model of pHi regulation in central CO2- chemoreception

In CO
₂
chemosensitive neurons, an increase in CO
₂
(hypercapnia) leads to a maintained reduction in intracellular pH (pH
_i
) while in non-chemosensitive neurons pH
_i
recovery is observed. The precise mechanisms for the differential regulation of pH
_i
recovery between these cell populations remain to be identified; however, studies have begun to explore the role of Na+/H+ exchange (NHE). Here we present the results of a mathematical model that explores pHi regulation in central CO, chemoreception, and in particular the role of the isoform NHE-5 (present in brainstem neurons). We found that NHE-5 kinetics leads to pHi recovery in response to simulated hypercapnia as we already reported for the isoforms NHE-1 and NHE-3. Further, we wanted to test whether our model can reproduce common experimental protocols like NH
₄

⁺
pre-pulse experiments designed to alter pH
_i
.