Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 293, Issue 3, Pages R1294-R1302Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00261.2007
Keywords
anion exchanger; sodium bicarbonate cotransporter; sodium hydrogen exchanger; acidosis; hypercapnia
Categories
Funding
- NICHD NIH HHS [HD 032573] Funding Source: Medline
- NINDS NIH HHS [NS 037756, NS 18400] Funding Source: Medline
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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 ( pHi) using a group of transmembrane proteins that specialize in acid- base transport. These acid- base transporters are important in adjusting pHi 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% CO2 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 CO2. Chronic CO2 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. CO2 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 pHi in the face of acidosis; and 2) the heterogeneous response of tissues to hypercapnia depends on the level of CO2 and development.
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