Effect of chronic elevated carbon dioxide on the expression of acid-base transporters in the neonatal and adult mouse

Abstract

Several pulmonary and neurological conditions, both in the newborn and adult, result in hypercapnia. This leads to disturbances in normal pH homeostasis. Most mammalian cells maintain tight control of intracellular pH (pH(i)) using a group of transmembrane proteins that specialize in acid-base transport. These acid-base transporters are important in adjusting pH(i) during acidosis arising from hypoventilation. We hypothesized that exposure to chronic hypercapnia induces changes in the expression of acid-base transporters. Neonatal and adult CD-1 mice were exposed to either 8% or 12% CO(2) for 2 wk. We used Western blot analysis of membrane protein fractions from heart, kidney, and various brain regions to study the response of specific acid-base transporters to CO(2). Chronic CO(2) increased the expression of the sodium hydrogen exchanger 1 (NHE1) and electroneutral sodium bicarbonate cotransporter (NBCn1) in the cerebral cortex, heart, and kidney of neonatal but not adult mice. CO(2) increased the expression of electrogenic NBC (NBCe1) in the neonatal but not the adult mouse heart and kidney. Hypercapnia decreased the expression of anion exchanger 3 (AE3) in both the neonatal and adult brain but increased AE3 expression in the neonatal heart. We conclude that: 1) chronic hypercapnia increases the expression of the acid extruders NHE1, NBCe1 and NBCn1 and decreases the expression of the acid loader AE3, possibly improving the capacity of the cell to maintain pH(i) in the face of acidosis; and 2) the heterogeneous response of tissues to hypercapnia depends on the level of CO(2) and development.

Molecular cloning and gene expression analysis in aquaculture science: a review focusing on respiration and immune responses in European sea bass (Dicentrarchus labrax)

“…Instead, the slow increase in NHE-1 mRNA in sea bass kidney during chronic hypercapnia (96 h) was consistent with results of studies in mammals that showed an increase in NHE-1 messenger during chronic metabolic acidosis in the kidney cortex (Soleimani et al 1995). Moreover, a recent scientific publication reported a significant increase in acid extruder protein levels (among which is NHE-1) and a decrease in acid loader proteins in kidney, brain, and heart of mice exposed to chronic hypercapnia; This is considered an adaptive response to attenuate intracellular acidosis induced by hypercapnia in this animal (Kanaan et al 2007).…”

Interaction of monocarboxylate transporter 4 with β1-integrin and its role in cell migration

“…It has been well established that cells rely on ionic transporters and exchangers to modulate both intracellular and extracellular pH (23,26,38,48). Much of this work has focused on a specific class of acid-base transporters, the sodium-proton exchangers (NHE).…”

Live-cell microscopy – tips and tools

“…1D,E; supplementary material Movie 4). These experiments emphasize that the presence of carbonate is important for many cellular processes, such as those related to the actions of Cl -and Na + exchangers, as well as co-transporters (Kanaan et al, 2007), and is not simply required to buffer the medium (Casey, 2006). All media should be supplemented with 25 mM HEPES to avoid adverse effects on cells due to pH changes, which can occur after approximately 5 minutes in the absence of CO 2 (not shown).…”