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.

• Authors: Amjad Kanaan, Robert M Douglas, Seth L Alper, Walter F Boron, Gabriel G Haddad
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 293 Issue 3 Pg. R1294-302 (Sep 2007) ISSN: 0363-6119 [Print] United States
• PMID: 17652362 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anion Transport Proteins
• Antibodies, Blocking
• Antiporters
• Carrier Proteins
• Cation Transport Proteins
• Membrane Proteins
• SLC4A Proteins
• Slc9a1 protein, mouse
• Sodium-Bicarbonate Symporters
• Sodium-Hydrogen Exchanger 1
• Sodium-Hydrogen Exchangers

Topics

• Animals
• Animals, Newborn (physiology)
• Anion Transport Proteins (metabolism)
• Antibodies, Blocking (pharmacology)
• Antiporters (metabolism)
• Blotting, Western
• Body Weight (physiology)
• Brain Chemistry (physiology)
• Carrier Proteins (metabolism)
• Cation Transport Proteins (antagonists & inhibitors, biosynthesis)
• Chronic Disease
• Hypercapnia (metabolism)
• Kidney (metabolism)
• Male
• Membrane Proteins (antagonists & inhibitors, biosynthesis)
• Mice
• Myocardium (metabolism)
• SLC4A Proteins
• Sodium-Bicarbonate Symporters (metabolism)
• Sodium-Hydrogen Exchanger 1
• Sodium-Hydrogen Exchangers (antagonists & inhibitors, biosynthesis)