ENaC and ROMK channels in the connecting tubule regulate renal K+ secretion

Abstract

We measured the activities of epithelial Na channels (ENaC) and ROMK channels in the distal nephron of the mouse kidney and assessed their role in the process of K+ secretion under different physiological conditions. Under basal dietary conditions (0.5% K), ENaC activity, measured as amiloride-sensitive currents, was high in cells at the distal end of the distal convoluted tubule (DCT) and proximal end of the connecting tubule (CNT), a region we call the early CNT (CNTe). In more distal parts of the CNT (aldosterone-sensitive portion [CNTas]), these currents were minimal. This functional difference correlated with alterations in the intracellular location of ENaC, which was at or near the apical membrane in CNTe and more cytoplasmic in the CNTas. ROMK activity, measured as TPNQ-sensitive currents, was substantial in both segments. A mathematical model of the rat nephron suggested that K+ secretion by the CNTe predicted from these currents provides much of the urinary K+ required for K balance on this diet. In animals fed a K-deficient diet (0.1% K), both ENaC and ROMK currents in the CNTe decreased by ∼50%, predicting a 50% decline in K+ secretion. Enhanced reabsorption by a separate mechanism is required to avoid excessive urinary K+ losses. In animals fed a diet supplemented with 3% K, ENaC currents increased modestly in the CNTe but strongly in the CNTas, while ROMK currents tripled in both segments. The enhanced secretion of K+ by the CNTe and the recruitment of secretion by the CNTas account for the additional transport required for K balance. Therefore, adaptation to increased K+ intake involves the extension of robust K+ secretion to more distal parts of the nephron.

The Post-Translational Modification Networking in WNK-Centric Hypertension Regulation and Electrolyte Homeostasis

“…Meanwhile, ROMK and ENaC activity increase in the downstream CCD. These data support the idea that a high-K + diet could increase the risk of hypertension due to overactivated sodium reabsorption channels [ 180 ]. Another study conducted in rats reported that heterozygous ROMK disruption may lead to reduced blood pressure and less severe renal injury.…”

Lessons learned about epithelial sodium channels from transgenic mouse models

“…In a recent study, Yang and coworkers studied ENaC and ROMK activities along the distal nephron on various K + diets. ENaC-dependent K + secretion shifted from the early CNT under basal to more distal parts of the CNT under increased K + intake [32 ▪▪ ].…”

A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls

“…Potassium is freely filtered through the glomerulus and into the nephrons. As the luminal fluid passes through the nephrons, various regulatory processes control how much K + is secreted or reabsorbed [7][8][9]. A schematic of renal K + handling is shown in Fig.…”

“…However, the distal tubule's capacity to reabsorb K + is limited (up to 3% of filtered K + in male rats), meaning that in times of drastically low K + intake, it is up to the downstream collecting duct to conserve K + via reabsorption [7,8].…”