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A mathematical model of pH i regulation in central CO 2 chemoreception
Author(s) -
Cordovez Juan M,
Clausen Chris,
Moore Leon C,
Solomon Irene C
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a916-d
Subject(s) - hypercapnia , intracellular ph , chemoreceptor , gene isoform , biophysics , sodium–hydrogen antiporter , amiloride , chemistry , intracellular , biochemistry , receptor , biology , sodium , acidosis , endocrinology , gene , organic chemistry
In CO 2 ‐chemosensitive neurons, 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 between these cell types remain to be identified, but studies are exploring the role of Na + /H + exchangers (NHE). Previously, we developed a mathematical model to investigate potential mechanisms of pH i regulation in response to simulated hypercapnia. We found that differences in pH i recovery between the two cell types could not be explained by differences between NHE1 and NHE3 isoforms. We have reformulated the model by incorporating equations describing passive electrodiffusion that adhere to the constant‐field assumption (previously, we used a linear equivalent‐circuit approach). Our new model confirms our previous results, and we also find that a third NHE isoform, NHE5 (also present in brainstem neurons), similarly produces pH i recovery in response to simulated hypercapnia. Further, in response to a simulated NH 4 + pre‐pulse protocol, pH i rapidly rises followed by acidification (consistent with experiments), and removal of the NH 4 + results in further acidification, followed by pH i recovery that can be inhibited by amiloride. Additional H + extrusion pathways as well as the role of the anion exchanger are being explored to identify other mechanisms involved in pH i regulation. Supported by DK66124 and NS045321