Expression of the Na-K-2Cl cotransporter by macula densa and thick ascending limb cells of rat and rabbit nephron

Nicholas Obermüller, Shanti Kunchaparty, David Ellison, Sebastian Bachmann

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Sodium and chloride transport by the macula densa and thick ascending limb of Henle's loop participates importantly in extracellular fluid volume homeostasis, urinary concentration and dilution, control of glomerular filtration, and control of renal hemodynamics. Transepithelial Na and Cl transport across the apical membrane of thick ascending limb (TALH) cells is mediated predominantly by a loop diuretic sensitive Na-K-2Cl cotransport pathway. The corresponding transport protein has recently been cloned. Functional studies suggest that the cotransporter is expressed by macula densa cells as well as by TALH cells. The current studies were designed to identify sites of Na-K-2Cl cotransporter expression along distal nephron in rabbit and rat. Non-isotopic high-resolution in situ hybridization, using an antisense probe for the apical form of the Na-K-2Cl cotransporter identified expression throughout the TALH, from the junction between inner and outer medulla to the transition to distal convoluted tubule. Expression by macula densa cells was confirmed by colocalization using markers specific for macula densa cells. First, Na-K-2Cl cotransporter mRNA was detected in macula densa cells that did not stain with anti-Tamm-Horsfall protein antibodies. Second, Na-K-2Cl cotransporter mRNA was detected in macula densa cells that show positive NADPH-diaphorase reaction, indicating high levels of constitutive nitric oxide synthase activity. In rat, levels of Na-K-2Cl cotransporter mRNA expression were similar in TALH and macula densa cells. In rabbit, expression levels were higher in macula densa cells than in surrounding TALH cells. The present data provide morphological support for a previously established functional concept that Na-K-2Cl cotransport at the TALH is accomplished by the expression of a well-defined cotransporter. At the macula densa, this transporter may establish a crucial link between tubular salt load and glomerular vascular regulation.

Original languageEnglish (US)
Pages (from-to)635-640
Number of pages6
JournalJournal of Clinical Investigation
Volume98
Issue number3
StatePublished - Aug 1 1996
Externally publishedYes

Fingerprint

Nephrons
Extremities
Rabbits
Messenger RNA
Uromodulin
Sodium Potassium Chloride Symporter Inhibitors
Loop of Henle
NADPH Dehydrogenase
Extracellular Fluid
Sodium Chloride
Nitric Oxide Synthase
In Situ Hybridization
Blood Vessels
Carrier Proteins
Homeostasis
Coloring Agents
Salts
Hemodynamics
Kidney
Membranes

Keywords

  • distal nephron
  • NADPH-diaphorase
  • nitric oxide
  • Tamm-Horsfall protein
  • tubulo-glomerular feedback

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Expression of the Na-K-2Cl cotransporter by macula densa and thick ascending limb cells of rat and rabbit nephron. / Obermüller, Nicholas; Kunchaparty, Shanti; Ellison, David; Bachmann, Sebastian.

In: Journal of Clinical Investigation, Vol. 98, No. 3, 01.08.1996, p. 635-640.

Research output: Contribution to journalArticle

Obermüller, Nicholas ; Kunchaparty, Shanti ; Ellison, David ; Bachmann, Sebastian. / Expression of the Na-K-2Cl cotransporter by macula densa and thick ascending limb cells of rat and rabbit nephron. In: Journal of Clinical Investigation. 1996 ; Vol. 98, No. 3. pp. 635-640.
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