Distal Convoluted Tubule Chloride Concentration is Modulated via Potassium Channels and Transporters.

Distal Convoluted Tubule Chloride Concentration is Modulated via Potassium Channels and Transporters. Am J Physiol Renal Physiol. 2020 Jul 27;: Authors: Su XT, Klett NJ, Sharma A, Allen CN, Wang WH, Yang CL, Ellison DH Abstract Cl--sensitive with-no-lysine kinase (WNK) plays a key role in regulating the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT). Cl- enters DCT cells through NCC and leaves the cell across the basolateral membrane via the Cl- channel ClC-Kb or a K-Cl cotransporter (KCC). While KCC is electroneutral, Cl- exit via ClC-Kb is electrogenic. Therefore, an alteration in DCT basolateral K+ channel activity is expected to influence Cl- movement across the basolateral membrane. Although a role for intracellular Cl- in the regulation of WNK and NCC has been established, intracellular Cl- concentrations ([Cl-]i) have not been directly measured in mammalian DCT. Therefore, to measure [Cl-]i in DCT cells, we have generated a transgenic mouse model expressing an optogenetic kidney-specific Cl-Sensor and measured Cl- fluorescent imaging in the isolated DCT. Basal measurements indicate that the mean [Cl-]i is approximately 7 mM. Stimulation of chloride exit with low chloride hypotonic solutions decreased [Cl-]i, whereas inhibition of KCC by DIOA or inhibition of ClC-Kb by NPPB increased [Cl-]i, suggesting roles for both KCC and ClC-Kb modulating [Cl-]i . Blocking the basolateral K+ cha...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research