Through a glass darkly: salt transport by the distal tubule

Abstract

The distal convoluted tubule (DCT) plays a central role in blood pressure and potassium homeostasis, as evidenced by diseases that occur when its function is modified. The paper by van der Lubbe and colleagues makes clear that angiotensin II itself increases the activity and abundance of the thiazide-sensitive Na-Cl cotransporter (NCC), independent of changes in circulating aldosterone. This Commentary provides additional perspective on that work.

Figure 1

Simplified scheme of regulation of thiazide-sensitive Na-Cl cotransporter (NCC) regulation. NCC is synthesized and then glycosylated (green fork) within the golgi apparatus (not shown, for clarity). The NCC then moves to and into the apical membrane, where it exists as a dimer. To be full active, NCC undergoes phosphorylation along its amino terminal cytoplasmic domain, mediated largely by SPAK, thereby permitting NaCl transport. Little is know about mechanisms of removal from the membrane. Arginine vasopressin (AVP), aldosterone (Aldo), and angiotensin II (Ang II) all stimulate NCC activity. Trafficking may be a rapid effect, modulated predominantly by AVP and Ang II. Phosphorylation may occur within the membrane, and is enhanced by all three factors.

Figure 2

Redrawn from data in the paper by van der Lubbe. Bar plot shows the effects of aldosterone (Aldo), angiotensin II (Ang II) and pressor dose Ang II (Ang II High) on abundance of the alpha subunit of ENaC, SPAK, and phosphorylated NCC. Note that all three interventions increase phosphorylated NCC, whereas only aldosterone increases ENaC abundance. Please see text for more details.