Potassium secretion and the regulation  of distal nephron K channels

K-selective channels in the luminal membranes of distal nephron segments form a key pathway for the secretion of K ions into the urine. This process is important to the control of K balance, particularly under conditions of normal or high K intake. This brief review will cover three issues: 1) the identification of apical K channels, 2) the role of these channels in the maintenance of K homeostasis, and 3) the role of aldosterone in this regulatory process. The large amount of literature on renal K transport has been elegantly summarized in a recent review in this journal [G. Giebisch. Am. J. Physiol.274 ( Renal Physiol. 43): F817–F833, 1998]. Here I will focus on a few prominent unsolved problems.

Download Full-text

Selective Proton-Mediated Transport by Electrogenic K+-Binding Macrocycles

Chemistry ◽

10.3390/chemistry2010003 ◽

2020 ◽

Vol 2 (1) ◽

pp. 11-21

Author(s):

Yu-Hao Li ◽

Shao-Ping Zheng ◽

Dawei Wang ◽

Mihail Barboiu

Keyword(s):

Ion Channels ◽

Therapeutic Agents ◽

K Channel ◽

Transport Activity ◽

Selective Activation ◽

K Channels ◽

High K ◽

Carbonyl Cyanide ◽

Self Assembled ◽

K Transport

Synthetic K+-binding macrocycles have potential as therapeutic agents for diseases associated with KcsA K+ channel dysfunction. We recently discovered that artificial self-assembled n-alkyl-benzoureido-15-crown-5-ether form selective ion-channels for K+ cations, which are highly preferred to Na+ cations. Here, we describe an impressive selective activation of the K+ transport via electrogenic macrocycles, stimulated by the addition of the carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP) proton carrier. The transport performances show that both the position of branching or the size of appended alkyl arms favor high transport activity and selectivity SK+/Na+ up to 48.8, one of the best values reported up to now. Our study demonstrates that high K+/Na+ selectivity obtained with natural KcsA K+ channels is achievable using simpler artificial macrocycles displaying constitutional functions.

Download Full-text

Identification and localization of BK-β subunits in the distal nephron of the mouse kidney

AJP Renal Physiology ◽

10.1152/ajprenal.00018.2007 ◽

2007 ◽

Vol 293 (1) ◽

pp. F350-F359 ◽

Cited By ~ 58

Author(s):

P. Richard Grimm ◽

Ruth M. Foutz ◽

Robert Brenner ◽

Steven C. Sansom

Keyword(s):

Immunohistochemical Staining ◽

Bk Channels ◽

Mouse Kidney ◽

Thick Ascending Limb ◽

Distal Nephron ◽

Rt Pcr ◽

Western Blots ◽

Nephron Segments ◽

High K ◽

Specific Localization

Large-conductance, Ca2+-activated K+ channels (BK), comprised of pore-forming α- and accessory β-subunits, secrete K+ in the distal nephron under high-flow and high-K+ diet conditions. BK channels are detected by electrophysiology in many nephron segments; however, the accessory β-subunit associated with these channels has not been determined. We performed RT-PCR, Western blotting, and immunohistochemical staining to determine whether BK-β1 is localized to the connecting tubule's principal-like cells (CNT) or intercalated cells (ICs), and whether BK-β2-4 are present in other distal nephron segments. RT-PCR and Western blots revealed that the mouse kidney expresses BK-β1, BK-β2, and BK-β4. Available antibodies in conjunction with BK-β1−/− and BK-β4−/− mice allowed the specific localization of BK-β1 and BK-β4 in distal nephron segments. Immunohistochemical staining showed that BK-β1 is localized in the CNT but not ICs of the connecting tubule. The localization of BK-β4 was discerned using an anti-BK-β4 antibody on wild-type tissue and anti-GFP on GFP-replaced BK-β4 mouse (BK-β4−/−) tissue. Both antibodies (anti-BK-β4 and anti-GFP) localized BK-β4 to the thick ascending limb (TAL), distal convoluted tubule (DCT), and ICs of the distal nephron. It is concluded that BK-β1 is narrowly confined to the apical membrane of CNTs in the mouse, whereas BK-β4 is expressed in the TAL, DCT, and ICs.

Download Full-text

Role of 20-HETE in mediating the effect of dietary K intake on the apical K channels in the mTAL

AJP Renal Physiology ◽

10.1152/ajprenal.2001.280.2.f223 ◽

2001 ◽

Vol 280 (2) ◽

pp. F223-F230 ◽

Cited By ~ 22

Author(s):

Ruimin Gu ◽

Yuan Wei ◽

Houli Jiang ◽

Michael Balazy ◽

Wenhui Wang

Keyword(s):

Gas Chromatography Mass Spectrometry ◽

K Channel ◽

Thick Ascending Limb ◽

Patch Clamp Technique ◽

Open Probability ◽

Deficient Diet ◽

K Channels ◽

Medullary Thick Ascending Limb ◽

High K

We have used the patch-clamp technique to study the effect of dietary K intake on the apical K channels in the medullary thick ascending limb (mTAL) of rat kidneys. The channel activity, defined by the number of channels in a patch and the open probability ( NP o), of the 30- and 70-pS K channels, was 0.18 and 0.11, respectively, in the mTAL from rats on a K-deficient diet. In contrast, NP o of the 30- and 70-pS K channels increased to 0.60 and 0.80, respectively, in the tubules from animals on a high-K diet. The concentration of 20-hydroxyeicosatetraenoic acid (20-HETE) measured with gas chromatography-mass spectrometry was 0.8 pg/μg protein in the mTAL from rats on a high-K diet and increased significantly to 4.6 pg/μg protein in the tubules from rats on a K-deficient diet. Addition of N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) or 17-octadecynoic acid (17-ODYA), agents that inhibit the formation of 20-HETE, had no significant effect on the activity of the 30-pS K channels. However, DDMS/17-ODYA significantly increased the activity of the apical 70-pS K channel from 0.11 to 0.91 in the mTAL from rats on a K-deficient diet. In contrast, inhibition of the cytochrome P-450 metabolism of arachidonic acid increased NP o from 0.64 to 0.81 in the tubules from animals on a high-K diet. Furthermore, the sensitivity of the 70-pS K channel to 20-HETE was the same between rats on a high-K diet and on a K-deficient diet. Finally, the pretreatment of the tubules with DDMS increased NP o of the 70-pS K channels in the mTAL from rats on a K-deficient diet to 0.76. We conclude that an increase in 20-HETE production is involved in reducing the activity of the apical 70-pS K channels in the mTAL from rats on a K-deficient diet.

Download Full-text

K(+)-induced inhibition of contractile force in rat skeletal muscle: role of active Na(+)-K+ transport

AJP Cell Physiology ◽

10.1152/ajpcell.1991.261.5.c799 ◽

1991 ◽

Vol 261 (5) ◽

pp. C799-C807 ◽

Cited By ~ 86

Author(s):

T. Clausen ◽

M. E. Everts

Keyword(s):

Rat Skeletal Muscle ◽

Uniform Size ◽

Muscle Work ◽

Standard Buffer ◽

High K ◽

Longus Muscle ◽

K Concentration ◽

K Transport ◽

Contractile Performance

During excitation, K+ is lost from the working muscle fibers, and interfiber K+ may reach 10-15 mM. This, in turn, may lead to depolarization and impairment of contractile performance. The significance of elevated interfiber K+ was assessed by exposing rat muscles of uniform size (25 mg) to buffer containing 12.5-15 mM K+ and studying the decline in contractile performance and its recovery following restoration of the K+ concentration of the standard buffer (5.9 mM). When active Na(+)-K+ transport was partially inhibited by ouabain (10(-6)-10(-5) M leading to relative occupancies of 28 and 84%, respectively), the decrease in force development induced by high K+ in soleus was considerably accelerated and recovery was delayed. Conversely, when active Na(+)-K+ transport was stimulated by epinephrine, the beta 2-agonist salbutamol, or insulin, the exposure to high K+ gave a much slower decline in force. The time until full inhibition was closely correlated to the rate of Na(+)-K+ pump-mediated 86Rb uptake (r = 0.98; P less than 0.005). Significant retardation of K(+)-induced force decline could be detected down to 10(-8) M epinephrine or salbutamol. After restoration of 5.9 mM K+, recovery was promoted by epinephrine and salbutamol but not by insulin. In extensor digitorum longus muscle, insulin reduced the rate of force decline induced by exposure to 15 mM K+. The results indicate that the Na(+)-K+ pump plays a major role in the maintenance of contractility during the physiological acute exposure to high extracellular K+ associated with muscle work.

Download Full-text

Expression of claudin-7 and -8 along the mouse nephron

AJP Renal Physiology ◽

10.1152/ajprenal.00384.2003 ◽

2004 ◽

Vol 286 (6) ◽

pp. F1063-F1071 ◽

Cited By ~ 141

Author(s):

Wing Y. Li ◽

Catherine L. Huey ◽

Alan S. L. Yu

Keyword(s):

Tight Junction ◽

Renal Tubule ◽

Basolateral Membrane ◽

Paracellular Permeability ◽

Mouse Kidney ◽

Integral Membrane Proteins ◽

Distal Nephron ◽

Nephron Segments ◽

Nephron Segment

Claudins are integral membrane proteins of the tight junction that determine the magnitude and selectivity of paracellular permeability in epithelial tissues. The mammalian renal tubule exhibits considerable heterogeneity in the permeability properties of its different segments. To determine the nephron segment localization of claudin-7 and -8, immunofluorescence staining of mouse kidney sections was performed using isoform-specific antibodies. Claudin-8 was found to be expressed primarily at the tight junction along the entire aldosterone-sensitive distal nephron and in the late segments of the thin descending limbs of long-looped nephrons. This pattern of expression is consistent with the putative role of claudin-8 as a paracellular cation barrier. By contrast, claudin-7 was found in the same nephron segments as claudin-8, but it was expressed primarily at the basolateral membrane.

Download Full-text

Renal Na-K-ATPase: its role in tubular sodium and potassium transport

AJP Renal Physiology ◽

10.1152/ajprenal.1982.242.3.f207 ◽

1982 ◽

Vol 242 (3) ◽

pp. F207-F219 ◽

Cited By ~ 14

Author(s):

A. I. Katz

Keyword(s):

Cation Transport ◽

Potassium Transport ◽

Secondary Active Transport ◽

Nephron Segments ◽

Single Nephron ◽

Acute Changes ◽

K Transport ◽

Sodium And Potassium ◽

Slow Turnover

Na-K-ATPase, the enzymatic equivalent of the sodium:potassium pump, is found in large amounts in the kidney, and this organ has figured prominently both as a source for the purification of the enzyme and as a target for the study of its properties. Located on the basolateral aspect of tubule cells, renal Na-K-ATPase plays a key role in the active translocation of Na and K across this membrane as well as in the "secondary active" transport of a number of other solutes. The activity of renal Na-K-ATPase varies in parallel with sustained changes in Na or K transport, indicating the participation of this enzyme in the chronic adaptation of the kidney to altered Na reabsorption or K secretory load. Because of its slow turnover, however, the role of Na-K-ATPase in the modulation of acute changes in cation transport is unclear. Several hormones and vanadate influence renal Na-K-ATPase activity, and their importance as potential physiologic regulators of this enzyme is examined. Most of the information on the renal enzyme has been obtained from studies using homogenates or subcellular fractions thereof, but more recently the development of tubule microdissection and microanalytic methods has made possible the study of Na-K-ATPase in single nephron segments. This approach has opened new possibilities for evaluating the role of this enzyme in kidney function by facilitating correlation of enzyme activity with transport events in the same structure and by enabling us to focus the study of Na-K-ATPase on discrete anatomic subdivisions of the functionally heterogeneous nephron.

Download Full-text

Role of luminal anion and pH in distal tubule potassium secretion

AJP Renal Physiology ◽

10.1152/ajprenal.00236.2002 ◽

2003 ◽

Vol 284 (2) ◽

pp. F381-F388 ◽

Cited By ~ 33

Author(s):

J. B. O. Amorim ◽

M. A. Bailey ◽

R. Musa-Aziz ◽

G. Giebisch ◽

G. Malnic

Keyword(s):

Distal Tubule ◽

Distal Nephron ◽

Progressive Reduction ◽

Perfusion Fluid ◽

Alkanoic Acid ◽

Channel Modulation ◽

Luminal Perfusion ◽

Potassium Secretion ◽

Permeant Anion

Potassium secretory flux ( J K) by the distal nephron is regulated by systemic and luminal factors. In the present investigation, J K was measured with a double-barreled K+ electrode during paired microperfusion of superficial segments of the rat distal nephron. We used control solutions (100 mM NaCl, pH 7.0) and experimental solutions in which Cl− had been replaced with a less permeant anion and/or pH had been increased to 8.0. J K increased when Cl− was replaced by either acetate (∼37%), sulfate (∼32%), or bicarbonate (∼62%), and also when the pH of the control perfusate was increased (∼26%). The majority (80%) of acetate-stimulated J K was Ba2+sensitive, but furosemide (1 mM) further reduced secretion (∼10% of total), suggesting that K+-Cl− cotransport was operative. Progressive reduction in luminal Cl−concentration from 100 to 20 to 2 mM caused increments in J K that were abolished by inhibitors of K+-Cl− cortransport, i.e., furosemide and [(dihydroindenyl)oxy]alkanoic acid. Increasing the pH of the luminal perfusion fluid also increased J K even in the presence of Ba2+, suggesting that this effect cannot be accounted for only by K+ channel modulation of K+ secretion in the distal nephron of the rat. Collectively, these data suggest a role for K+-Cl− cotransport in distal nephron K+ secretion.

Download Full-text

The Role of 20-Hete in Mediating the Effect of Diatary K Intake on the Apical K Channels in the Mtal.

Hypertension ◽

10.1161/hyp.36.suppl_1.710-c ◽

2000 ◽

Vol 36 (suppl_1) ◽

pp. 710-710

Author(s):

WenHui Wang ◽

RuiMin Gu ◽

Yuan Wei ◽

Michael Balazy ◽

Houli Jiang

Keyword(s):

K Channel ◽

Thick Ascending Limb ◽

Channel Activity ◽

Patch Clamp Technique ◽

Deficient Diet ◽

K Channels ◽

Medullary Thick Ascending Limb ◽

A Value ◽

High K

P95 We have used the patch clamp technique to study the effect of dietary-K intake on the apical K channels in the medullary thick ascending limb (mTAL) of rat kidneys. The channel activity, defined by NPo, of the 30 pS and 70 pS K channel was 0.18 and 0.11 in the mTAL from rats on a K-deficient diet, respectively. In contrast, NPo of the 30 pS and the 70 pS K channels increased to 0.60 and 0.80 in the tubules from animals on a high-K diet, respectively. We have also used GC/MC to measure the intracellular production of 20-hydroxyeicosanotetraenoic acid (20-HETE) in the mTAL. The concentration of 20-HETE was 0.8 pg/μg protein in the mTAL from rats on a high-K diet and increased significantly to 4.6 pg/μg protein in the tubules from rats on a K-deficient diet. Addition of N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) or 17-octadecynoic acid (17ODYA), agents which inhibit the formation of 20-HETE, had no significant effect on the activity of the 30 pS K channels. However, DDMS/17ODYA significantly increased the activity of the apical 70 pS K channel from 0.11 to 0.91 in the mTAL from rats on a K-deficient diet. In contrast, inhibition of the cytochrome P450 metabolism of arachidonic acid (AA) increased NPo from 0.64 to 0.81 in the tubules from animals on a high-K diet. Furthermore, the concentration of 20-HETE required to block the channel activity by 50% was the same in the mTAL from rats on a high K diet as that on a K-deficient diet. This indicates that the diminished response of the 70 pS K channel to the inhibition of P450 metabolism of AA is not the result of decreasing 20-HETE sensitivity in the mTAL from rats on a high K diet. Finally, the pretreatment of the tubules with DDMS increased NPo of the 70 pS K channels in the mTAL from rats on a K-deficient diet to 0.76, a value which is not significantly different from the NPo in the tubules from rats on a high-K diet. We conclude that an increase in 20-HETE production is involved in reducing the activity of the apical 70 pS K channels in the mTAL from rats on a K-deficient diet.

Download Full-text