The Journal of Physiology has recently published an article entitled “Multiple acid-base and electrolyte disturbances upregulate NBCn1, NBCn2, IRBIT and L-IRBIT in the mTAL” from Professor Li-Ming Chen’s group in the School of Life Science and Technology at HUST.
The Na+-HCO3– cotransporters NBCn1 (encoded by SLC4A7) and NBCn2 (encoded by SLC4A10) are expressed in the basolateral membrane of medullary thick ascending limb of renal tubule. IRBIT (encoded by AHCYL1) and L-IRBIT (encoded by AHCYL2) are two interacting partners of NBCn1 and NBCn2. The authors found that both IRBIT and L-IRBIT could powerfully stimulate the activities of the renal forms of NBCn1 and NBCn2 heterologously expressed in Xenopus oocytes. The authors found that dietary challenges of NH4Cl, NaHCO3, or NaCl all increase the abundance of NBCn1 and NBCn2 in the outer medulla. Moreover, the three challenges generally produce parallel increases in the abundance of IRBIT and L-IRBIT in the outer medulla. The authors propose that:
1. Under metabolic acidosis (too much acid in the body), renal NBCn1 and NBCn2 are upregulated to promote NH4+ shunting in the mTAL, therefore increasing renal acid excretion (Model A).
2. Under metabolic alkalosis (too much base in the body), renal NBCn1 and NBCn2 are upregulated to inhibit HCO3– reabsorption in the mTAL by counteracting the action of basolateral AE2 (encoded by SLC4A2), therefore increasing renal base excretion.
3. Under high salt diet (too much salt in the body), renal NBCn1 and NBCn2 are upregulated to inhibt NaCl reabsorption in concert with AE2, therefore increassing renal NaCl excretion.
4. Under the three challenges, the role of NBCn1 and NBCn2 in the mTAL are further strengthened by IRBIT and L-IRBIT.
The study supports the notion that NBCn1 and NBCn2 plus their activators IRBIT and L-IRBIT are at the nexus of the regulatory pathways for multiple renal transport processes. The findings about the regulation of renal NaCl reabsorption is of particular interest. It is well known that renal NaCl reabsorption is very important for the fine tuning of blood pressure. Genetic studies have shown that both SLC4A7 encoding NBCn1 and SLC4A2 encoding AE2 are associated with hypertension. The study from the Chen group indicates that the development of hypertension associated with dysfunction of SLC4A7 or SLC4A2 likely includes a renal component.
It is said that this new paper is a follow-up study of a previous one from the same group which was published on Journal of the American Society of Nephrology, a leading kidney journal in the field. This previous paper, which was feattured, as research highlight, by Nature Reviews Nephrology, made very interesting findings that led to the formulation of a new theory that the apical NBCn2 in the proximal tubule mediates HCO3– reabsorption. This new theory challenged the traditional doctrine well-documented in physiology textbooks.
