Differential expression and cellular distribution of mRNAs encoding alpha- and beta-isoforms of Na(+)-K(+)-ATPase in...

We have used in situ hybridization histochemistry with isoform-specific, digoxigenin-labeled cRNA probes to characterize systematically the cellular distribution of mRNAs encoding alpha- and beta-subunit isoforms of the Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the normal rat kidney. Transcripts encoding the alpha 1-, alpha 2-, alpha 3-, beta 1-, and beta 2-subunits were detected in virtually all of the nephron segments, with prominent hybridization signal in the S3 segment of the proximal tubule, the cortical and medullary thick ascending limb of Henle's loop, the distal convoluted tubule, the cortical collecting duct along its entire length, and the renal pelvic epithelium. Several differences in the cell-specific pattern of expression of the various isoforms were observed. Among the alpha-isoforms, the alpha 3-subunit appeared to be preferentially expressed in the glomerular podocytes and mesangial cells, papillary interstitial cells, and renal pelvic epithelium. The beta-isoforms also differed in their distribution pattern, with the beta 1-subunit expressed to a greater degree in the glomerulus and renal pelvic epithelium and the beta 2-subunit preferentially expressed in the papillary interstitial cells and papillary surface epithelium. The detection and expression pattern of alpha- and beta-subunit mRNAs in structures throughout the kidney is compatible with the possibility of six structurally unique Na(+)-K(+)-ATPase isozymes and suggests a potentially greater role for isozymes comprised of the alpha 2-, alpha 3-, and beta 2-subunits in renal sodium and potassium transport.