Regulation of Renal Potassium Secretion: Molecular Mechanisms

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Summary

A new understanding of renal potassium balance has emerged as the molecular underpinnings of potassium secretion have become illuminated, highlighting the key roles of apical potassium channels, renal outer medullary potassium channel (ROMK) and Big Potassium (BK), in the aldosterone-sensitive distal nephron and collecting duct. These channels act as the final-regulated components of the renal potassium secretory machinery. Their activity, number, and driving forces are precisely modulated to ensure potassium excretion matches dietary potassium intake. Recent identification of the underlying regulatory mechanisms at the molecular level provides a new appreciation of the physiology and reveals a molecular insight to explain the paradoxic actions of aldosterone on potassium secretion. Here, we review the current state of knowledge in the field.

Section snippets

Principal Cell

Our understanding of potassium secretion is built on elegant physiological studies in the collecting duct, revealing the transport properties of the principal cell12, 13 (Fig. 1). According to current understanding, the potassium secretory process by the cortical collecting duct (CCD) principal cell and similar cells in the connecting tubule (CNT) and late distal tubule is mediated by a two-step transcellular transport mechanism. Potassium actively is transported from the interstitium across

A Secretory Potassium Channel Pas De Deux in the ASDN

The identification of the apical potassium channels at the molecular level, complemented by insights from patch-clamp studies in the ASDN and classic microperfusion studies, have made it possible to understand how aldosterone and other regulatory factors collude at the cellular and molecular levels to affect the rate of urinary K excretion in concert with the requirements of potassium balance. Two types of apical membrane potassium channels, ROMK43 (Kir1.1,44 the product of KCNJ1 gene) and the

Flow-Dependent Potassium Secretion and BK Channels

Renal potassium secretion is well established to be dependent on tubular flow rate. It rapidly increases with an increase in tubular flow and decreases when flow rate diminishes.70, 71, 72, 73, 74 The relationship is important for understanding the actions of aldosterone on potassium secretion. In fact, the physiologic uncoupling of aldosterone-dependent K+ secretion from Na+ reabsorption has been explained traditionally by the Na+- and flow-dependent nature of potassium secretion. For example,

Regulation of ROMK Activity

Patch-clamp studies showed that the regulated increase in ROMK channel function in response to a dietary potassium load was brought about by alterations in the number of functional channels at the apical surface rather than by graded changes in the open probability.90 In principle, gating mechanisms that switch resident apical channels completely “on” from a completely “off” mode may be responsible. Certainly, ROMK channels are regulated in such a fashion because channel opening requires

Summary

Solutions to the aldosterone paradox are complex and multifactorial, but current evidence indicates that reciprocal regulation of potassium secretory channels and the thiazide-sensitive sodium chloride co-transporter in the distal nephron plays a key role. In addition, regulation of proton/potassium ATPase, which controls potassium absorption, could potentially contribute6, 7, 8 as recent studies have implicated important roles of kallikrein,6 desoxy­cortico­sterone,8 and progesterone7 in the

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