High baseline ROMK activity in the mouse late distal convoluted and early connecting tubule probably contributes to aldosterone-independent K+ secretion

Nesterov V, Bertog M, Korbmacher C (2022)


Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 322

Pages Range: F42-F54

Journal Issue: 1

DOI: 10.1152/AJPRENAL.00252.2021

Abstract

The renal outer medullary K+ channel (ROMK) is colocalized with the epithelial Na+ channel (ENaC) in the late distal convoluted tubule (DCT2), connecting tubule (CNT), and cortical collecting duct (CCD). ENaC-mediated Na+ absorption generates the electrical driving force for ROMK-mediated tubular K+ secretion, which is critically important for maintaining renal K+ homeostasis. ENaC activity is aldosterone dependent in the late CNT and early CCD (CNT/CCD) but aldosterone independent in the DCT2 and early CNT (DCT2/CNT). This suggests that under baseline conditions with low plasma aldosterone, ROMK-mediated K+ secretion mainly occurs in the DCT2/CNT. Therefore, we hypothesized that baseline ROMK activity is higher in the DCT2/CNT than in the CNT/CCD. To test this hypothesis, patch-clamp experiments were performed in the DCT2/CNT and CNT/CCD microdissected from mice maintained on a standard diet. In single-channel recordings from outside-out patches, we detected typical ROMK channel activity in both the DCT2/CNT and CNT/CCD and confirmed that ROMK is the predominant K+ channel in the apical membrane. Amiloride-sensitive and tertiapin-sensitive whole-cell currents were determined to assess ENaC and ROMK activity, respectively. As expected, baseline amiloride-sensitive current was high in the DCT2/CNT (∼370 pA) but low in the CNT/CCD (∼60 pA). Importantly, tertiapin-sensitive current was significantly higher in the DCT2/CNT than in the CNT/CCD (∼810 vs. ∼350 pA). We conclude that high ROMK activity in the DCT2/CNT is critical for aldosterone-independent renal K+ secretion under baseline conditions. A low-K+ diet significantly reduced ENaC but not ROMK activity in the DCT2/CNT. This suggests that modifying ENaC activity in the DCT2/CNT plays a key regulatory role in adjusting renal K+ excretion to dietary K+ intake.

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How to cite

APA:

Nesterov, V., Bertog, M., & Korbmacher, C. (2022). High baseline ROMK activity in the mouse late distal convoluted and early connecting tubule probably contributes to aldosterone-independent K+ secretion. American Journal of Physiology-Renal Physiology, 322(1), F42-F54. https://doi.org/10.1152/AJPRENAL.00252.2021

MLA:

Nesterov, Viatcheslav, Marko Bertog, and Christoph Korbmacher. "High baseline ROMK activity in the mouse late distal convoluted and early connecting tubule probably contributes to aldosterone-independent K+ secretion." American Journal of Physiology-Renal Physiology 322.1 (2022): F42-F54.

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