The Na+ Driven Anion Exchanger, NDAE1

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.

With our cloning of an electrogenic Na+/HCO–3 cotransporter (NBC; i.e., SLC4A4), we found that NBC and the anion exchangers (AEs; i.e., SLC4A1- SLC4A3) form a bicarbonate transporter superfamily (BTS) . More recently three groups have reported unique full-length cDNAs which are additions to the BTS: NBC-2 from retina , an electroneutral NBC (NBCN1) , and NBC-3 (SLC4A7) from muscle . Functional data for NBC-2 has not been reported. NBCN1 is an electroneutral Na+/HCO–3 cotransporter that is partially blocked by DIDS . NBC-3 is currently characterized as a DIDS-insensitive, EIPA-sensitive, Na+/HCO–3 cotransporter whose electrical nature is not yet known. It is presently unclear whether these clones arise from separate genes or are splicing isoforms. Of the NBC clones reported, none are Cl- dependent or transport Cl-.

Physiologically two other HCO–3 transporters are known: a K+/HCO–3 cotransporter and a Na+-dependent Cl--HCO–3 exchanger. Here we report the cloning and characterization of a cation-coupled Cl--HCO–3 exchanger and a physiologically unique BTS member from Drosophila. When expressed in Xenopus oocytes, this membrane protein mediates the transport of Cl-, Na+, H+, and HCO3–, but does not require HCO–3. Transport is blocked by the stilbene DIDS and may not be strictly electroneutral. Our expression data suggest this Na+ driven anion exchanger (NDAE1, GenBank AF047468) is responsible for the Na+ dependent Cl--HCO–3 exchange activity characterized in neurons , kidney , and fibroblasts.

NDAE1 transports HCO3– and base equivalents, when expressed in Xenopus oocytes. We have also demonstrated that Na+ and Cl- are counter-transported (see Model and NDAE1 Cloning). All transport modes are blocked by the stilbene, DIDS. Additionally, diphenyl carboxylic acid (DPC) and niflumic acid block transport.

Recently, we have developed an antibody to NDAE1 (Sciortino et al. Am. J. Physiol. Cell Physiol.281: C449-463, 2001). We have used this NDAE1 antibody to follow NDAE1 protein through Drosophila development and determine the epithelial protein location in larval and adult tissues.

Am. J. Physiol. Cell Physiology cover : July -Dec, 2001

More recent studies are using Drosophila genetics and microelectrode physiology to discern an NDAE1 phenotype. These studies are in collaboration with Dr. Peter Harte in Genetics at CWRU.