These studies are carried out in collaboration with Dr. David B. Mount at Harvard
Ionic homeostasis is key to normal function of most biological systems. This regulation is especially important for tissues with highly specialized functions, such as the central nervous system (CNS), digestive tract, respiratory tract, and urinary system. Active transport of ions by ATPases (pumps) maintains ionic gradients and aid ion channels in "setting" the membrane potential. Secondary active transporters make use of one or more aspects of the membrane electrochemical gradient to specifically move ions and nutrients into and out of cellular compartments.
The proteins encoded by slc26 gene family are proving quite interesting. The members seem anion promiscuous in their mediated transport. Many transport Cl-, others transport SO42-, some transport formate and oxylate, and several can transport HCO3–.
In collaboration with Dr. David Mount's Lab at Brigham & Women's Hospital, we are characterizing several new members of this gene family, especially with regard to their HCO3– transport. Of particular interest is that slc26a6, found at the brush border membrane of the renal proximal tubule, is capable of Cl-/formate exchange, Cl-/oxylate exchange, and Cl-/HCO3– exchange. In fact, slc26a6 is most likely the Cl-/formate exchanger of the proximal tubule [Knauf et al., PNAS, USA 98: 9425–9430, 2001]. Our recent electrophysiology experiments indicate that slc26a6 is a new type of Cl-/HCO3– exchanger, i.e., slc26a6 is an electrogenic Cl-/HCO3– exchanger [Xie et al., Am. J. Physiol. Renal Physiol. 283: F826-838, 2002]. Thus, understanding the biophysics of these new transport systems allows us to better describe transport processes in various epithelial cell and tissue types.