Pendrin gene ablation alters ENaC subcellular distribution and open probability.

This study explored whether the intercalated cell Cl(-)/HCO3 (-) exchanger, pendrin, modulates ENaC function by changing channel open probability and/or channel density. To do so, we measured ENaC subunit subcellular distribution by immunohistochemistry, single channel recordings in split open cortical collecting ducts (CCDs), as well as transepithelial voltage (VT), and Na(+) absorption (JNa) in CCDs from aldosterone-treated wild type and pendrin null mice. Because pendrin gene ablation reduced 70 more than 85 kD γ ENaC band density, we asked if pendrin gene ablation interferes with ENaC cleavage. We observed that ENaC cleaving protease application (trypsin) increased the lumen-negative VT in pendrin null but not in wild type mice, which raised the possibility that pendrin gene ablation blunts ENaC cleavage, thereby reducing open probability. In mice harboring wild type ENaC, pendrin gene ablation reduced ENaC-mediated Na(+) absorption by reducing channel open probability as well as by reducing channel density through changes in subunit total protein abundance and subcellular distribution. Further experiments employed mice with blunted ENaC endocytosis and degradation (Liddle's Syndrome) to explore the significance of pendrin-dependent changes in ENaC open probability. In Liddle's mice, pendrin gene ablation did not change ENaC subunit total protein abundance, subcellular distribution or channel density, but markedly reduced channel open probability. We conclude that in mic...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research