**2.3 Potassium movement in thick ascending loop of Henle**

In this part of nephron, ~25% of filtered sodium is reabsorbed together with ~15% of the filtered potassium. Transcellular sodium and potassium transport is achieved by the Na+K+2Cl- cotransporter (NKCC2) in the apical membrane, driven by the basolateral Na+K+ATPase pump. Alternative names for NKCC2 include the bumetanide sensitive cotransporter, (BSC). NKCC2 is exclusively expressed in kidney tissue and is encoded by *SLC12A1* gene (Simon, et al., 1996a). The NKCC2 transporter may also transport ammonium ions, which compete with potassium ions.

 Potassium entering the cell via NKCC2 is recycled back into tubule lumen via the apical membrane channel, ROMK1 (Simon, et al., 1996b), generating a lumen positive potential driving paracellular resorption of calcium and magnesium. Tight junction proteins, such as paracellin 1, mediate this divalent cation transport. ROMK1, also known as a KCNJ, is an ATPase sensitive potassium channel. Functional coupling of ROMK1 with NKCC2 is essential for NaCl reabsorption. Chloride exits the basolateral membrane of the TAL via the CLC chloride channel, CLC-KB, which is co-expressed with the subunit Barttin.

### **2.4 The distal convoluted tubule**

The distal convoluted tubule is responsible for ~8% of filtered sodium reabsorption. This is achieved via an apical Na+Cl- cotransporter (NCCT, alias the thiazide sensitive sodium chloride transporter). This transporter is regulated by a group of serine-threonine protein kinases, incluidng WNK4. In healthy individuals, WNK4 inhibits NCCT function by reducing its expression on the membrane.

Recent data has suggested that potassium channels control DCT function. An apically expressed potassium channel Kv1.1 is postulated to stabilise the luminal membrane potential in this nephron segment (Glaudemans, et al., 2009). and facilitates effective magnesium transport via the apical TRPM6 magnesium channel. At the basolateral membrane of the DCT a potassium channel Kir4.1 is thought to allow potassium recycling, allowing maintenance of the basolateral Na+K+ATPase activity, the driving force for NaCl reabsorption via NCCT in this nephron segment (Bockenhauer, et al., 2009, Scholl, et al., 2009).

## **2.5 The collecting ducts**

90 Basic Nephrology and Acute Kidney Injury

patients with chronic kidney disease. Generalized defects in proximal tubule handling of solutes result in Fanconi syndrome syndrome. Specific proximal tubular handling defects leading to hypokalemia include proximal renal tubular acidosis, and have been recently

Potassium may be secreted in the thin descending loops of Henle that penetrate the inner medulla, whilst the thin ascending loop is permeable to sodium and potassium and allows

The thin ascending limbs of the loops of Henle (among other nephron segments) express the CLC-KA chloride channel, with its subunit Barttin. Polymorphisms in *CLCNKA* have recently been associated with a hyperreninemic hyperaldosteronism, implicating a key role for this channel in regulating renal salt handling and determining a set point for renin and

In this part of nephron, ~25% of filtered sodium is reabsorbed together with ~15% of the filtered potassium. Transcellular sodium and potassium transport is achieved by the Na+K+2Cl- cotransporter (NKCC2) in the apical membrane, driven by the basolateral Na+K+ATPase pump. Alternative names for NKCC2 include the bumetanide sensitive cotransporter, (BSC). NKCC2 is exclusively expressed in kidney tissue and is encoded by *SLC12A1* gene (Simon, et al., 1996a). The NKCC2 transporter may also transport ammonium

 Potassium entering the cell via NKCC2 is recycled back into tubule lumen via the apical membrane channel, ROMK1 (Simon, et al., 1996b), generating a lumen positive potential driving paracellular resorption of calcium and magnesium. Tight junction proteins, such as paracellin 1, mediate this divalent cation transport. ROMK1, also known as a KCNJ, is an ATPase sensitive potassium channel. Functional coupling of ROMK1 with NKCC2 is essential for NaCl reabsorption. Chloride exits the basolateral membrane of the TAL via the

The distal convoluted tubule is responsible for ~8% of filtered sodium reabsorption. This is achieved via an apical Na+Cl- cotransporter (NCCT, alias the thiazide sensitive sodium chloride transporter). This transporter is regulated by a group of serine-threonine protein kinases, incluidng WNK4. In healthy individuals, WNK4 inhibits NCCT function by

Recent data has suggested that potassium channels control DCT function. An apically expressed potassium channel Kv1.1 is postulated to stabilise the luminal membrane potential in this nephron segment (Glaudemans, et al., 2009). and facilitates effective magnesium transport via the apical TRPM6 magnesium channel. At the basolateral membrane of the DCT a potassium channel Kir4.1 is thought to allow potassium recycling, allowing maintenance of the basolateral Na+K+ATPase activity, the driving force for NaCl reabsorption via NCCT in this nephron segment (Bockenhauer, et al., 2009, Scholl, et

CLC chloride channel, CLC-KB, which is co-expressed with the subunit Barttin.

reviewed elsewhere (Fry &Karet, 2007).

angiotensin levels (Cappola, et al., 2011).

ions, which compete with potassium ions.

**2.4 The distal convoluted tubule** 

al., 2009).

reducing its expression on the membrane.

some uptake.

**2.2 Potassium movement in the thin loop of Henle** 

**2.3 Potassium movement in thick ascending loop of Henle** 

The connecting tubules, initial collecting tubule and the cortical collecting duct, are major sites of regulated potassium secretion. Indeed, potassium secretion in these nephron segments may be upregulated to exceed the filtered load of potassium. In addition, if potassium reabsorption is required, this part of the nephron and regions of the medullary collecting duct may reabsorb potassium. In the cortical collecting duct two important cell types mediate potassium transport: principal cells and intercalated cells.

In principal cells, sodium entry occurs via selective sodium channels (ENaCs), located on apical membrane. Potassium secretion in these cells occurs by a transcellular movement of potassium, mediated by a basolateral Na+K+ATPase pump and apical ROMK potassium channels. Potassium secretion is directly linked to sodium entry via ENaC.

The distribution of ENaC channels within the apical membrane is regulated by effects of aldosterone on the mineralocorticoid receptor. The ENaC channel has three subunits: alpha, beta and gamma encoded by genes *SCNN1A*, *SCNN1B* and *SCNN1C.* Alpha-intercalated cells in the cortical collecting duct mediate potassium reabsorption. An apical H+K+ATPase pump allows potassium reabsorption coupled to proton excretion, whilst an apical proton pump transports hydrogen ions into the lumen. In states of potassium depletion, there is upregulation of the apical H+K+ATPase pump in alpha intercalated cells.
