scholarly journals TRPV4 as a flow sensor in flow-dependent K+ secretion from the cortical collecting duct

2007 ◽  
Vol 292 (2) ◽  
pp. F667-F673 ◽  
Author(s):  
Junichi Taniguchi ◽  
Shuichi Tsuruoka ◽  
Atsuko Mizuno ◽  
Jun-ichi Sato ◽  
Akio Fujimura ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Basolateral Membrane ◽  
Cortical Collecting Duct ◽  
Urine Production ◽  
K Secretion ◽  
Distal Tubules ◽  
Transient Receptor

The transient receptor vanilloid-4 (TRPV4) is a mechanosensitive, swell-activated cation channel that is abundant in the renal distal tubules. Immunolocalization studies, however, present conflicting data as to whether TRPV4 is expressed along the apical and/or basolateral membranes. To disclose the role of TRPV4 in flow-dependent K+ secretion in distal tubules in vivo, urinary K+ excretion and net transports of K+ and Na+ in the cortical collecting duct (CCD) were measured with an in vitro microperfusion technique in TRPV4 +/+ and TRPV4 −/− mice. Both net K+ secretion and Na+ reabsorption were flow dependently increased in the CCDs isolated from TRPV4 +/+mice, which were significantly enhanced by a luminal application of 50 μM 4α-phorbol-12,13-didecanoate (4αPDD), an agonist of TRPV4. No flow dependence of net K+ and Na+ transports or effects of 4αPDD on CCDs were observed in TRPV4 −/− mice. A basolateral application of 4αPDD had little effect on these ion transports in the TRPV4 +/+ CCDs, while the luminal application did. Urinary K+ excretion was significantly smaller in TRPV4 −/− than in TRPV4 +/+ mice when urine production was stimulated by a venous application of furosemide. These observations suggested an essential role of the TRPV4 channels in the luminal or basolateral membrane as flow sensors in the mechanism underlying the flow-dependent K+ secretion in mouse CCDs.

Cellular actions of cAMP on HCO3(-)-secreting cells of rabbit CCD: dependence on in vivo acid-base status

1994 ◽  
Vol 266 (4) ◽  
pp. F528-F535 ◽  
Author(s):  
C. Emmons ◽  
J. B. Stokes
Keyword(s):  
Anion Exchanger ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Disulfonic Acid ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Acid Base ◽  
Acid Base Status

HCO3- secretion by cortical collecting duct (CCD) occurs via beta-intercalated cells. In vitro CCD HCO3- secretion is modulated by both the in vivo acid-base status of the animal and by adenosine 3',5'-cyclic monophosphate (cAMP). To investigate the mechanism of cAMP-induced HCO3- secretion, we measured intracellular pH (pHi) of individual beta-intercalated cells of CCDs dissected from alkali-loaded rabbits perfused in vitro. beta-Intercalated cells were identified by demonstrating the presence of an apical anion exchanger (cell alkalinization in response to removal of lumen Cl-). After 180 min of perfusion to permit decrease of endogenous cAMP, acute addition of 0.1 mM 8-bromo-cAMP or 1 microM isoproterenol to the bath caused a transient cellular alkalinization (> 0.20 pH units). In the symmetrical absence of either Na+, HCO3-, or Cl-, cAMP produced no change in pHi. Basolateral dihydrogen 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (0.1 mM) for 15 min before cAMP addition also prevented this alkalinization. In contrast to the response of cells from alkali-loaded rabbits, addition of basolateral cAMP to CCDs dissected from normal rabbits resulted in an acidification of beta-intercalated cells (approximately 0.20 pH units). The present studies demonstrate the importance of the in vivo acid-base status of the animal in the regulation of CCD HCO3- secretion by beta-intercalated cells. The results identify the possible existence of a previously unrecognized Na(+)-dependent Cl-/HCO3- exchanger on the basolateral membrane of beta-intercalated cells in alkali-loaded rabbits.

H(+)-K(+)-ATPase in rabbit cortical collecting duct B-type intercalated cell

1996 ◽  
Vol 270 (3) ◽  
pp. F518-F530 ◽  
Author(s):  
I. D. Weiner ◽  
A. E. Milton
Keyword(s):  
B Cell ◽  
Apical Membrane ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Cortical Collecting Duct ◽  
Intercalated Cell ◽  
Acid Load ◽  
Phi Regulation

The role of H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase) in the cortical collecting duct (CCD) B-type intercalated cell (B cell) is unclear. This study examined whether H(+)-K(+)-ATPase contributes to B cell intracellular pH (pHi) regulation and, if so, whether it is present at the apical or basolateral membrane. B cell Na(+)-independent pHi recovery from an acid load was only partially inhibited by peritubular N-ethylmaleimide (NEM). Complete inhibition required combining peritubular NEM either with luminal Sch-28080 or with luminal K+ removal. In contrast, neither peritubular Sch-28080 nor peritubular K+ removal altered pHi regulation. Tomato lectin, which binds to the gastric H(+)-K(+)-ATPase beta-subunit, labeled the B cell apical membrane. We conclude that the rabbit CCD B cell possesses an apical H(+)-K(+)-ATPase that plays an important role in pHi recovery from an in vitro acid load.

Effect of vasopressin on Na+-K+-ATPase activity in rat cortical collecting duct

1987 ◽  
Vol 253 (5) ◽  
pp. F874-F879 ◽  
Author(s):  
K. Tomita ◽  
A. Owada ◽  
Y. Iino ◽  
N. Yoshiyama ◽  
T. Shiigai
Keyword(s):  
Atpase Activity ◽  
Time Course ◽  
Collecting Duct ◽  
Cortical Collecting Duct ◽  
Henle's Loop ◽  
K Secretion ◽  
Medullary Collecting Duct ◽  
Hydrolysis Of

Vasopressin (V) causes a sustained increase in Na reabsorption and K secretion in isolated cortical collecting ducts (CCD) from rats. Because increased Na reabsorption may be associated with increased Na+-K+-ATPase activity, we investigated effects of V, given either in vivo or in vitro, on Na+-K+-ATPase activity in isolated nephron segments of rats. Na+-K+-ATPase activities were measured by coupling the hydrolysis of ATP to the production of a fluorescent nucleotide. In addition to CCD, other microdissected structures were medullary thick ascending limbs of Henle's loop, cortical thick ascending limbs of Henle's loop, and outer medullary collecting duct. To determine the time course of the response, Na+-K+-ATPase activities were measured in CCD 1 h, 3 h, 1 day, 3 days, and 7 days after intramuscular administrations of V. There was a significant increase in Na+-K+-ATPase activity in CCD after in vivo V administration for 7 days but not in any other segment. The activities increased after 3 days of administration of V. For in vitro experiments, CCD were incubated with 10(-6) M V for 1-3 h. Na+-K+-ATPase activities did not change after 1- or 3-h exposure of V in CCD in vitro. We conclude that prolonged V administration in vivo increases Na+-K+-ATPase activity in CCD. Because, in vitro exposure to V does not increase Na+-K+-ATPase activity, we conclude that rapid V-dependent increases in Na and K transport previously demonstrated in isolated perfused tubules are not dependent on a change in maximal Na+-K+-ATPase activity.

Total CO2 transport in rat cortical collecting duct in chloride-depletion alkalosis

1990 ◽  
Vol 258 (4) ◽  
pp. F848-F853 ◽  
Author(s):  
J. D. Gifford ◽  
K. Sharkins ◽  
J. Work ◽  
R. G. Luke ◽  
J. H. Galla
Keyword(s):  
Peritoneal Dialysis ◽  
Metabolic Alkalosis ◽  
Collecting Duct ◽  
Bicarbonate Transport ◽  
Cortical Collecting Duct ◽  
Co2 Transport ◽  
Chloride Depletion

Previous studies in chloride-depletion metabolic alkalosis (CDA) generated by intraperitoneal dialysis have suggested major alterations in chloride and bicarbonate transport beyond the distal convoluted tubule. To investigate the possible role of the cortical collecting duct (CCD) in the pathophysiology of CDA, isolated CCD segments were perfused in vitro from either control (CON) rats dialyzed against Ringer-bicarbonate or those made alkalotic by peritoneal dialysis with 0.15 M NaHCO3. Tubules from CDA animals secreted CO2 for greater than or equal to 3 h after dissection (-22.4 +/- 7.2 pmol.mm-1.min-1) compared with CON tubules that absorbed CO2 (18.3 +/- 4.2 pmol.mm-1.min-1). Replacement of luminal chloride with gluconate in the perfusate abolished net total CO2 (tCO2) secretion in tubules from CDA animals (from -21.5 +/- 4.5 to -2.7 +/- 2.3 pmol.mm-1.min-1) but did not alter net tCO2 absorption in tubules from CON animals. In contrast, removal of bath chloride increased net tCO2 secretion (-12.1 +/- 2.9 to -26.1 +/- 3.6 pmol.mm-1.min-1) in CDA tubules, whereas net tCO2 flux was altered from absorption to secretion in CON tubules (15.5 +/- 4.0 to -13.6 +/- 9.2 pmol.mm-1.min-1). These results demonstrate that 1) CDA generated in vivo within 45 min results in stable net tCO2 secretion in vitro up to 240 min in the CCD; 2) luminal chloride is necessary for tCO2 secretion; 3) the shift of net tCO2 flux from absorption to secretion in CON tubules in vitro was not sustained in contrast to CDA tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Opposing actions of Per1 and Cry2 in the regulation of Per1 target gene expression in the liver and kidney

2013 ◽  
Vol 305 (7) ◽  
pp. R735-R747 ◽  
Author(s):  
Jacob Richards ◽  
Sean All ◽  
George Skopis ◽  
Kit-Yan Cheng ◽  
Brandy Compton ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Target Genes ◽  
Collecting Duct ◽  
Sodium Reabsorption ◽  
Cortical Collecting Duct ◽  
Liver And Kidney ◽  
Dependent Mechanism

Mounting evidence suggests that the circadian clock plays an integral role in the regulation of many physiological processes including blood pressure, renal function, and metabolism. The canonical molecular clock functions via activation of circadian target genes by Clock/Bmal1 and repression of Clock/Bmal1 activity by Per1–3 and Cry1/2. However, we have previously shown that Per1 activates genes important for renal sodium reabsorption, which contradicts the canonical role of Per1 as a repressor. Moreover, Per1 knockout (KO) mice exhibit a lowered blood pressure and heavier body weight phenotype similar to Clock KO mice, and opposite that of Cry1/2 KO mice. Recent work has highlighted the potential role of Per1 in repression of Cry2. Therefore, we postulated that Per1 potentially activates target genes through a Cry2-Clock/Bmal1-dependent mechanism, in which Per1 antagonizes Cry2, preventing its repression of Clock/Bmal1. This hypothesis was tested in vitro and in vivo. The Per1 target genes αENaC and Fxyd5 were identified as Clock targets in mpkCCDc14 cells, a model of the renal cortical collecting duct. We identified PPARα and DEC1 as novel Per1 targets in the mouse hepatocyte cell line, AML12, and in the liver in vivo. Per1 knockdown resulted in upregulation of Cry2 in vitro, and this result was confirmed in vivo in mice with reduced expression of Per1. Importantly, siRNA-mediated knockdown of Cry2 and Per1 demonstrated opposing actions for Cry2 and Per1 on Per1 target genes, supporting the potential Cry2-Clock/Bmal1-dependent mechanism underlying Per1 action in the liver and kidney.

scholarly journals Role of NKCC in BK channel-mediated net K+ secretion in the CCD

2011 ◽  
Vol 301 (5) ◽  
pp. F1088-F1097 ◽  
Author(s):  
Wen Liu ◽  
Carlos Schreck ◽  
Richard A. Coleman ◽  
James B. Wade ◽  
Yubelka Hernandez ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Bk Channels ◽  
Bk Channel ◽  
Taqman Assay ◽  
Specific Cell ◽  
Cortical Collecting Duct ◽  
Ph Indicator ◽  
Transport Pathway ◽  
K Secretion

Apical SK/ROMK and BK channels mediate baseline and flow-induced K secretion (FIKS), respectively, in the cortical collecting duct (CCD). BK channels are detected in acid-base transporting intercalated (IC) and Na-absorbing principal (PC) cells. Although the density of BK channels is greater in IC than PC, Na-K-ATPase activity in IC is considered inadequate to sustain high rates of urinary K secretion. To test the hypothesis that basolateral NKCC in the CCD contributes to BK channel-mediated FIKS, we measured net K secretion ( JK) and Na absorption ( JNa) at slow (∼1) and fast (∼5 nl·min−1·mm−1) flow rates in rabbit CCDs microperfused in vitro in the absence and presence of bumetanide, an inhibitor of NKCC, added to the bath. Bumetanide inhibited FIKS but not basal JK, JNa, or the flow-induced [Ca2+]i transient necessary for BK channel activation. Addition of luminal iberiotoxin, a BK channel inhibitor, to bumetanide-treated CCDs did not further reduce JK. Basolateral Cl removal reversibly inhibited FIKS but not basal JK or JNa. Quantitative PCR performed on single CCD samples using NKCC1- and 18S-specific primers and probes and the TaqMan assay confirmed the presence of the transcript in this nephron segment. To identify the specific cell type to which basolateral NKCC is localized, we exploited the ability of NKCC to accept NH4+ at its K-binding site to monitor the rate of bumetanide-sensitive cytosolic acidification after NH4+ addition to the bath in CCDs loaded with the pH indicator dye BCECF. Both IC and PC were found to have a basolateral bumetanide-sensitive NH4+ entry step and NKCC1-specific antibodies labeled the basolateral surfaces of both cell types in CCDs. These results suggest that BK channel-mediated FIKS is dependent on a basolateral bumetanide-sensitive, Cl-dependent transport pathway, proposed to be NKCC1, in both IC and PC in the CCD.

Effect of insulin on potassium secretion in rabbit cortical collecting ducts

1992 ◽  
Vol 262 (1) ◽  
pp. F30-F35 ◽  
Author(s):  
H. Furuya ◽  
K. Tabei ◽  
S. Muto ◽  
Y. Asano
Keyword(s):  
Collecting Duct ◽  
Dependent Manner ◽  
Cortical Collecting Duct ◽  
Plasma Insulin Concentration ◽  
Concentration Dependent Manner ◽  
K Secretion ◽  
Potassium Secretion ◽  
Transepithelial Voltage ◽  
K Transport

Insulin is known to play an important role in the regulation of extrarenal K homeostasis. Previous clearance studies have shown that insulin decreases urinary K excretion, but the responsible nephron segments have not been identified. In this microperfusion study, in vitro, the effect of insulin on K transport in the cortical collecting duct (CCD), which is thought to be an important segment for regulation of the final urinary K excretion, was investigated. Basolateral insulin (10(-6) M) significantly inhibited net K secretion by 20% (mean JK = -26.2 +/- 4.2 peq.mm-1.min-1 for controls compared with -21.1 +/- 3.4 with insulin, P less than 0.001) and depolarized the transepithelial voltage (VT, from -14.6 +/- 3.5 to -10.8 +/- 3.5 mV, P less than 0.005), recovery did not occur over 60 min. Insulin (10(-11)-10(-5) M) depressed K secretion and depolarized the VT in a concentration-dependent manner. The half-maximal concentration was 5 x 10(-10) M, which is within the physiological range of plasma insulin concentration. In tubules of deoxycorticosterone acetate-treated rabbits, insulin also produced a significant fall in K secretion (from -43.4 +/- 7.5 to -36.1 +/- 5.7 peq.mm-1.min-1, P less than 0.05). Although luminal Ba (2 mM) decreased K secretion (from -14.4 +/- 2.9 to -7.0 +/- 1.7 peq.mm-1.min-1), basolateral insulin (10(-6) M) inhibited K secretion further (to -4.7 +/- 1.3 peq.mm-1.min-1, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Deoxycorticosterone-stimulated bicarbonate secretion in rabbit cortical collecting ducts: effects of luminal chloride removal and in vivo acid loading

1985 ◽  
Vol 249 (2) ◽  
pp. F205-F212 ◽  
Author(s):  
J. Garcia-Austt ◽  
D. W. Good ◽  
M. B. Burg ◽  
M. A. Knepper
Keyword(s):  
Collecting Duct ◽  
High Rate ◽  
Bicarbonate Secretion ◽  
Cortical Collecting Duct ◽  
Acid Base ◽  
Urinary Ph ◽  
Collecting Ducts ◽  
Acid Loading

To assess the role of cortical collecting duct bicarbonate secretion in the regulation of net acid excretion, we have sought to identify what factors influence the secretion rate. Net and unidirectional bicarbonate fluxes were measured in isolated perfused cortical collecting ducts from deoxycorticosterone-treated rabbits. The collecting ducts secreted bicarbonate at 11-24 pmol X mm-1 X min-1, confirming the high rate seen in earlier studies. Oral acid loading (50 mM NH4Cl drinking water) completely inhibited the net bicarbonate secretion. The bath-to-lumen flux was markedly reduced with acid loading, but the lumen-to-bath flux changed very little. In tubules from rabbits treated with deoxycorticosterone (but not NH4Cl), luminal chloride replacement with either sulfate or gluconate completely and reversibly inhibited the net bicarbonate secretion. The bath-to-lumen flux was greatly inhibited, but there was little change in the lumen-to-bath flux. We conclude: 1) High rates of bicarbonate secretion can be induced in rabbit cortical collecting ducts by chronic treatment of the animals with deoxycorticosterone. 2) When deoxycorticosterone-treated rabbits were made acidotic by oral administration of NH4Cl, the bicarbonate secretion was prevented, indicating that the systemic acid-base state of the animal may be an important factor regulating bicarbonate secretion. 3) Replacement of chloride in the lumen with sulfate inhibits bicarbonate secretion in the cortical collecting duct, an effect which may explain in part the decrease in urinary pH in response to sulfate infusions in mineralocorticoid-stimulated animals.

Stimulation of total CO2 flux by 10% CO2 in rabbit CCD: role of an apical Sch-28080- and Ba-sensitive mechanism

1994 ◽  
Vol 267 (1) ◽  
pp. F114-F120 ◽  
Author(s):  
X. Zhou ◽  
C. S. Wingo
Keyword(s):  
Collecting Duct ◽  
Co2 Flux ◽  
K Channel ◽  
Co2 Absorption ◽  
Cortical Collecting Duct ◽  
Atpase Inhibitor ◽  
Contrast Exposure ◽  
Stimulation Of

These studies examine the effect of ambient PCO2 on net bicarbonate (total CO2) absorption by the in vitro perfused cortical collecting duct (CCD) from K-replete rabbits and the mechanism responsible for this effect. Exposure to 10% CO2 increased net bicarbonate flux (total CO2 flux, JtCO2) by 1.8-fold (P < 0.005), and this effect was inhibited by luminal 10 microM Sch-28080, an H-K-adenosinetriphosphatase (H-K-ATPase) inhibitor. In contrast, exposure to 10% CO2 significantly decreased Rb efflux, and this decrement in Rb efflux was blocked by luminal 2 mM Ba, a K channel blocker. Thus transepithelial tracer Rb flux did not increase upon exposure to 10% CO2 as we have observed in this segment under K-restricted conditions. The observation that 10% CO2 increased net bicarbonate absorption without a change in absorptive Rb flux suggested that 10% CO2 increased apical K recycling. To test this hypothesis, we examined whether luminal Ba inhibited the stimulation of luminal acidification induced by 10% CO2. If apical K exit were necessary for full activation of proton secretion, then inhibiting K exit should indirectly affect the stimulation of JtCO2 by 10% CO2. In fact, the effect of 10% CO2 on JtCO2 in the presence of 2 mM luminal Ba was quantitatively indistinguishable from the effect of 10% CO2 on JtCO2 in the presence of 10 microM luminal Sch-28080.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional characterization of alpha- and beta-intercalated cell types in rabbit cortical collecting duct

1991 ◽  
Vol 261 (3) ◽  
pp. F377-F385 ◽  
Author(s):  
H. Furuya ◽  
M. D. Breyer ◽  
H. R. Jacobson
Keyword(s):  
Collecting Duct ◽  
Basolateral Membrane ◽  
Functional Characterization ◽  
Cell Types ◽  
Disulfonic Acid ◽  
Cortical Collecting Duct ◽  
Electrical Measurements ◽  
Collecting Ducts

Single-cell electrical measurements and spectrophotometric determinations of intracellular pH were used to determine unique features of alpha- and beta-intercalated cells (alpha-IC, beta-IC) in in vitro perfused rabbit cortical collecting ducts (CCD). pHi rose in alpha-IC and fell in beta-IC after bath Cl- removal. Luminal Cl- removal did not change pHi of alpha-IC, but pHi of beta-IC rose by 0.36 +/- 0.01 pH units. Cl- concentration-dependent recovery of beta-IC pHi revealed a Cl- Km of 18.7 mM for the luminal Cl(-) -HCO3- exchanger. Measurements of basolateral membrane voltage (Vbl) also showed two IC cell types. Removal of luminal Cl- did not change Vbl in alpha-IC, whereas Vbl hyperpolarized by a mean of 73.2 +/- 3.5 mV in beta-IC. Reducing bath Cl- depolarized both alpha- and beta-IC Vbl. In alpha-IC a large repolarization of 39.8 +/- 5.2 mV followed acute depolarization after bath Cl- removal. Reducing bath HCO3- (constant CO2) had little effect on beta-IC Vbl, whereas alpha-IC Vbl depolarized by 5.2 +/- 0.7 mV. Reducing luminal HCO3- in the absence of luminal Cl- produced a 17.6 +/- 1.8 mV depolarization in beta-IC. This change was independent of luminal Na+ and was not blocked by luminal 10(-4) M 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In beta-IC, Vbl was not altered by either bath or lumen DIDS in the presence of luminal Cl-. However, when luminal Cl- was removed, luminal DIDS reversibly depolarized Vbl by 9.6 +/- 2.9 mV.(ABSTRACT TRUNCATED AT 250 WORDS)

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