Primary structure and functional expression of a novel gastrointestinal isoform of the rat Na/H exchanger

A cDNA encoding a new isoform of the rat Na/H exchanger (NHE) family has been identified by cross-hybridization with an NHE-1 cDNA probe. The 3.9-kilobase stomach cDNA encodes a protein of 813 amino acids with an M(r) of 91,296. The amino acid sequence of the protein, termed NHE-2, is 42% identical to NHE-1, 36% identical to NHE-3, and 57% identical to NHE-4. Na/H exchanger-deficient Chinese hamster ovary cells that were transfected with an expression construct containing the complete coding sequence of this cDNA exhibit amiloride-sensitive, H+-dependent 22Na+ influx, demonstrating that the protein it encodes is a functional Na/H exchanger. Northern hybridization analyses show that the corresponding mRNA is expressed predominantly in small intestine, colon, and stomach, with much lower levels present in skeletal muscle, kidney, brain, testis, uterus, heart, and lung. This suggests that NHE-2 plays an important role in gastrointestinal physiology and functions in many other organ systems as well.