Premium
pH i Regulation In Central CO 2 ‐Chemosensitive And Non‐Chemosensitive Cells: A Mathematical Model
Author(s) -
Cordovez Juan M,
Clausen Chris,
Moore Leon C,
Solomon Irene C
Publication year - 2006
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.20.4.a786-c
Subject(s) - hypercapnia , intracellular ph , biophysics , amiloride , sodium–hydrogen antiporter , chemistry , chemoreceptor , intracellular , acidosis , biochemistry , biology , sodium , receptor , endocrinology , organic chemistry
Numerous studies have suggested that a decrease in intracellular pH (pH i ) is the primary stimulus for CO 2 sensing in central CO 2 chemoreceptors. In CO 2 chemosensitive neurons, an increase in CO 2 (hypercapnia) leads to a maintained reduction in pH i while in non‐chemosensitive neurons pH i recovery is observed. We developed a mathematical model to evaluate the roles of intrinsic buffering capacity, Na + /H + exchange (NHE), and HCO 3 − /Cl − exchange (AE) on pH i regulation in response to simulated hypercapnic acidosis. The cell model incorporates conservation of mass and electroneutrality constraints, kinetic models of the Na + /K + ‐ATPase, AE, NHE3 isoform (believed to play a primary role in CO 2 sensing), and passive permeation pathways for ions, nonelectrolytes, and H 2 O. H + buffering (both inside and out) is handled by multiple buffer species all subject to the isohydric principle. In response to simulated hypercapnia, the model predicts pH i responses that are consistent with observations in non‐chemosensitive cells, including a pH i recovery mechanism that is dependent on NHE (based on simulation of amiloride effects). The model also demonstrates that inhibition of NHE is sufficient to decrease pH i in the absence of increased CO 2 and that the pH i fall during simulated hypercapnia is exacerbated. Additional H + extrusion pathways need to be explored to identify other mechanisms involved in pH i regulation in CO 2 chemosensitive neurons. Supported by DK66124