Distal convoluted tubule

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Abstract

The distal convoluted tubule (DCT) is a short nephron segment, interposed between the macula densa and collecting duct. Even though it is short, it plays a key role in regulating extracellular fluid volume and electrolyte homeostasis. DCT cells are rich in mitochondria, and possess the highest density of Na+/K+-ATPase along the nephron, where it is expressed on the highly amplified basolateral membranes. DCT cells are largely water impermeable, and reabsorb sodium and chloride across the apical membrane via electroneurtral pathways. Prominent among this is the thiazide-sensitive sodium chloride cotransporter, target of widely used diuretic drugs. These cells also play a key role in magnesium reabsorption, which occurs predominantly, via a transient receptor potential channel (TRPM6). Human genetic diseases in which DCT function is perturbed have provided critical insights into the physiological role of the DCT, and how transport is regulated. These include Familial Hyperkalemic Hypertension, the salt-wasting diseases Gitelman syndrome and EAST syndrome, and hereditary hypomagnesemias. The DCT is also established as an important target for the hormones angiotensin II and aldosterone; it also appears to respond to sympathetic-nerve stimulation and changes in plasma potassium. Here, we discuss what is currently known about DCT physiology. Early studies that determined transport rates of ions by the DCT are described, as are the channels and transporters expressed along the DCT with the advent of molecular cloning. Regulation of expression and activity of these channels and transporters is also described; particular emphasis is placed on the contribution of genetic forms of DCT dysregulation to our understanding.

Original languageEnglish (US)
Pages (from-to)45-98
Number of pages54
JournalComprehensive Physiology
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2015

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Nephrons
Member 3 Solute Carrier Family 12
Gitelman Syndrome
Wasting Syndrome
Transient Receptor Potential Channels
Inborn Genetic Diseases
Membranes
Extracellular Fluid
Ion Transport
Medical Genetics
Molecular Cloning
Aldosterone
Diuretics
Sodium Chloride
Angiotensin II
Magnesium
Electrolytes
Potassium
Mitochondria
Homeostasis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Distal convoluted tubule. / McCormick, James (Jim); Ellison, David.

In: Comprehensive Physiology, Vol. 5, No. 1, 01.01.2015, p. 45-98.

Research output: Contribution to journalArticle

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