Mechanism underlying flow stimulation of sodium absorption in the mammalian collecting duct

2006 ◽  
Vol 291 (3) ◽  
pp. F663-F669 ◽  
Author(s):  
Tetsuji Morimoto ◽  
Wen Liu ◽  
Craig Woda ◽  
Marcelo D. Carattino ◽  
Yuan Wei ◽  
...  
Keyword(s):  
Flow Rate ◽  
Membrane Trafficking ◽  
Collecting Duct ◽  
Extracellular Fluid ◽  
Brefeldin A ◽  
Sodium Absorption ◽  
Laminar Shear Stress ◽  
Open Probability ◽  
Flow Rates ◽  
Fast Flow

Vectorial Na+ absorption across the aldosterone-sensitive distal nephron plays a key role in the regulation of extracellular fluid volume and blood pressure. Within this nephron segment, Na+ diffuses from the urinary fluid into principal cells through an apical, amiloride-sensitive, epithelial Na+ channel (ENaC), which is considered to be the rate-limiting step for Na+ absorption. We have reported that increases in tubular flow rate in microperfused rabbit cortical collecting ducts (CCDs) lead to increases in net Na+ absorption and that increases in laminar shear stress activate ENaC expressed in oocytes by increasing channel open probability. We therefore examined whether flow stimulates net Na+ absorption ( JNa) in CCDs by increasing channel open probability or by increasing the number of channels at the apical membrane. Both baseline and flow-stimulated JNa in CCDs were mediated by ENaC, as JNa was inhibited by benzamil. Flow-dependent increases in JNa were observed following treatment of tubules with reagents that altered membrane trafficking by disrupting microtubules (colchicine) or Golgi (brefeldin A). Furthermore, reducing luminal Ca2+ concentration ([Ca2+]) or chelating intracellular [Ca2+] with BAPTA did not prevent the flow-dependent increase in JNa. Extracellular trypsin has been shown to activate ENaC by increasing channel open probability, and we observed that trypsin significantly enhanced JNa when tubules were perfused at a slow flow rate. However, trypsin did not further enhance JNa in CCDs perfused at fast flow rates. Similarly, the shear-induced increase in benzamil-sensitive JNa in oocytes expressing protease resistance ENaC mutants was similar to that of controls. Our results suggest the rise in JNa accompanying increases in luminal flow rates reflects an increase in channel open probability.

Adaptation of distal tubule and collecting duct to increased Na delivery. II. Na+ and K+ transport

1988 ◽  
Vol 255 (6) ◽  
pp. F1269-F1275 ◽  
Author(s):  
B. A. Stanton ◽  
B. Kaissling
Keyword(s):  
Tap Water ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Extracellular Fluid ◽  
Distal Tubule ◽  
Sodium Absorption ◽  
Transport Capacity ◽  
Volume Depletion ◽  
Osmotic Minipump ◽  
Sodium Uptake

This study was conducted to determine whether a chronic increase in sodium delivery to, and sodium uptake by, the distal tubule stimulates the transport capacity of this tubular segment. To increase the rate of sodium delivery to the distal tubule, furosemide (12 mg/day) was administered continuously to rats by osmotic minipump for 6 days. Volume depletion was prevented by giving the animals a drinking solution containing 0.8% NaCl and 0.1% KCl. Control animals were given vehicle (0.9% NaCl) by osmotic minipump and tap water to drink. All animals were adrenalectomized and given replacement doses of aldosterone (0.5 microgram.100 g-1.day-1) and dexamethasone (1.2 microgram.100 g-1.day-1) to eliminate changes in adrenal corticosteroid levels. Furosemide was withdrawn 12 h before sodium and potassium transport rates were measured in distal tubules by in vivo microperfusion. We found that increased sodium uptake dramatically enhanced the transport capacity of the distal tubule. Sodium absorption rose from 71.7 to 316.7 pmol.min-1.mm-1, and potassium secretion increased from 30.7 to 73.7 pmol.min-1.mm-1. This response was accompanied by an increase in cell and mitochondrial volume and by proliferation of the basolateral membrane of distal convoluted cells, connecting tubule cells, and principal cells in the distal tubule. We conclude that a chronic increase in sodium uptake by the distal tubule, independent of alterations in extracellular fluid volume and aldosterone levels, stimulates the transport capacity of this nephron segment in part by inducing specific alterations in cell ultrastructure.

Potassium transport in the distal tubule and collecting duct of the rat

1975 ◽  
Vol 229 (5) ◽  
pp. 1403-1409 ◽  
Author(s):  
HJ Reineck ◽  
RW Osgood ◽  
TF Ferris ◽  
JH Stein
Keyword(s):  
Flow Rate ◽  
Collecting Duct ◽  
Distal Tubule ◽  
Potassium Transport ◽  
Distal Convoluted Tubule ◽  
Potassium Excretion ◽  
Flow Rates ◽  
Urinary Potassium ◽  
Potassium Secretion ◽  
Tubular Flow

Because of recent conflicting results, micropuncture studies were performed to clarify the respective role of the distal convoluted tubule and collecting duct in the regulation of urinary potassium excretion. Five groups of Sprague-Dawley rats were studied: group I, hydropenia (n = 10); group II, Ringer loading (n = 7); group III, acute KC1 loading (n = 6); group IV, mannitol diuresis (n = 6); group V, KC1 infusion during mannitol diuresis (n = 7). Early and late distal tubules were identified with intravenous injections of lissamine green. In each animal net secretion of potassium occurred along the distal convoluted tubule, and a direct relationship between distal tubular flow rate and potassium secretion was observed. The magnitude of potassium secretion at high distal tubular flow rates was dependent on the model studied. Potassium transport beyond the distal tubule was evaluated by comparing end distal potassium delivery and fractional potassium excretion. At low urinary flow rates net reabsorption was observed, whereas at higher flow rates no net transport occurred. Thus, flow rate along the collecting duct may be a major determinant of urinary potassium excretion.

scholarly journals Mechanoregulation of BK channel activity in the mammalian cortical collecting duct: role of protein kinases A and C

2009 ◽  
Vol 297 (4) ◽  
pp. F904-F915 ◽  
Author(s):  
Wen Liu ◽  
Yuan Wei ◽  
Peng Sun ◽  
Wen-Hui Wang ◽  
Thomas R. Kleyman ◽  
...  
Keyword(s):  
Flow Rate ◽  
Collecting Duct ◽  
Bk Channel ◽  
Slow Flow ◽  
Cortical Collecting Duct ◽  
Flow Rates ◽  
Calphostin C ◽  
Flow Stimulation ◽  
Slow Flow Rate ◽  
Stimulation Of

Flow-stimulated net K secretion ( JK) in the cortical collecting duct (CCD) is mediated by an iberiotoxin (IBX)-sensitive BK channel, and requires an increase in intracellular Ca2+ concentration ([Ca2+]i). The α-subunit of the reconstituted BK channel is phosphorylated by PKA and PKC. To test whether the BK channel in the native CCD is regulated by these kinases, JK and net Na absorption ( JNa) were measured at slow (∼1) and fast (∼5 nl·min−1·mm−1) flow rates in rabbit CCDs microperfused in the presence of mPKI, an inhibitor of PKA; calphostin C, which inhibits diacylglycerol binding proteins, including PKC; or bisindolylmaleimide (BIM) and Gö6976, inhibitors of classic and novel PKC isoforms, added to luminal (L) and/or basolateral (B) solutions. L but not B mPKI increased JK in CCDs perfused at a slow flow rate; a subsequent increase in flow rate augmented JK modestly. B mPKI alone or with L inhibitor abolished flow stimulation of JK. Similarly, L calphostin C increased JK in CCDs perfused at slow flow rates, as did calphostin C in both L and B solutions. The observation that IBX inhibited the L mPKI- and calphostin C-mediated increases in JK at slow flow rates implicated the BK channel in this K flux, a notion suggested by patch-clamp analysis of principal cells. The kinase inhibited by calphostin C was not PKC as L and/or B BIM and Gö6976 failed to enhance JK at the slow flow rate. However, addition of these PKC inhibitors to the B solution alone or with L inhibitor blocked flow stimulation of JK. Interpretation of these results in light of the effects of these inhibitors on the flow-induced elevation of [Ca2+]i suggests that the principal cell apical BK channel is tonically inhibited by PKA and that flow stimulation of JK in the CCD is PKA and PKC dependent. The specific targets of the kinases remain to be identified.

PHOTOCHEMICAL SEPARATION OF MERCURY ISOTOPES: IV. THE REACTION OF Hg2026(3P1) ATOMS, PHOTOEXCITED IN NATURAL MERCURY VAPOR, WITH METHYL CHLORIDE AND ISOPROPYL CHLORIDE

1959 ◽  
Vol 37 (8) ◽  
pp. 1315-1327 ◽  
Author(s):  
K. R. Osborn ◽  
H. E. Gunning
Keyword(s):  
Flow Rate ◽  
Room Temperature ◽  
Methyl Chloride ◽  
Mercury Vapor ◽  
Progressive Increase ◽  
Temperature Data ◽  
Third Body ◽  
Flow Rates ◽  
Fast Flow ◽  
Static Conditions

A detailed investigation has been made of the reaction of Hg2026(3P1) atoms, photoexcited in natural mercury vapor (HgN), with methyl chloride, at room temperature. Data are also reported on the reaction with isopropyl chloride as substrate. Hg202 enrichment in the calomel product is taken as evidence of its formation in the primary quenching reaction.Under static conditions the methyl chloride reaction was found to form calomel with the natural Hg202 abundance (29.8%). With increasing flow rate a progressive increase in Hg202 abundance was observed. Maximum enrichments were found at fast flow rates, low substrate pressures, and high values for the absorbed light intensity (IA). The most highly enriched calomel obtained in this study contained 50.4% Hg202. With increasing IA, a corresponding increase in flow rate was required to achieve maximum Hg202 enrichment. The addition of propylene or butene-1 to the methyl chloride stream was found to result in a slight decrease in Hg202 abundance over that for the pure substrate.The isotopically specific aspects of the reaction are explained in terms of the sequence:[Formula: see text]where M represents a third body, including the wall. The decrease in enrichment observed at high substrate pressures is shown to be due to Lorentz-broadening effects on the hyperfine absorption contours of HgN. The failure to obtain enrichment under static conditions is explained by the depletion in Hg202 of the HgN in the cell through reaction [1].The investigation shows that there are two primary processes operative in the mercury-6(3P1)-photosensitized decomposition of alkyl chlorides, in one of which calomel is formed. These processes presumably involve a common short-lived intermediate R—Cl—Hg.

Postnatal maturation of potassium transport in rabbit cortical collecting duct

1994 ◽  
Vol 266 (1) ◽  
pp. F57-F65 ◽  
Author(s):  
L. M. Satlin
Keyword(s):  
Flow Rate ◽  
Collecting Duct ◽  
Cortical Collecting Duct ◽  
Flow Rates ◽  
Postnatal Maturation ◽  
Significant Linear Correlation ◽  
Potassium Secretion ◽  
Tubular Flow ◽  
Neonatal Kidney

Clearance studies in newborns demonstrate low rates of urinary excretion of potassium, suggesting that the neonatal kidney contributes to the conservation of potassium necessary for growth. Because the cortical collecting duct (CCD) is a primary site for potassium secretion in the adult, we sought to examine the transport capacity of this segment for potassium during postnatal maturation. CCDs isolated from rabbits of various ages (5-6 animals/age group) were microperfused in vitro with solutions simulating plasma. The concentrations of potassium in samples of collected fluid, measured by helium glow photometry, were used to calculate net transport. At a flow rate of approximately 1.6 nl.min-1 x mm-1 net potassium secretion was absent at birth, first became evident at 4 wk of age (-11.08 +/- 2.39 pmol.min-1 x mm-1), and increased sharply thereafter to reach mature rates (-23.08 +/- 3.47 pmol.min-1 x mm-1; P < 0.05) by 6 wk of age. To determine whether low distal tubular flow rates limit net potassium secretion in the neonate, we perfused CCDs at two or more flow rates in the 0.5–5 nl.min-1 x mm-1 range. In CCDs taken from animals > or = 6 wk of age, potassium secretion showed a significant linear correlation with flow rate (y = -10.0x - 7.45; r = 0.87; n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)

Flow-dependent transport processes: filtration, absorption, secretion

1982 ◽  
Vol 243 (1) ◽  
pp. F1-F11 ◽  
Author(s):  
F. S. Wright
Keyword(s):  
Flow Rate ◽  
Transport Process ◽  
Driving Force ◽  
Transport Processes ◽  
Sodium Absorption ◽  
Flow Rates ◽  
Proximate Cause ◽  
Flow Dependence ◽  
Dependent Change ◽  
Dependent Transport

To define aspects common to different flow-dependent renal transport processes, four examples of such transport processes are considered: glomerular filtration, distal potassium secretion, ascending limb sodium absorption, and proximal fluid absorption. For each example the phenomenon of flow dependence is documented and the mechanism underlying this behavior is explored. Two general types of flow dependence are recognized: dissipative and generative. The first three processes are examples of dissipative flow dependence. In each a flow-sensitive component of the driving force for transport is generated upstream from the site of transport, the transport process tends to dissipate its driving force, and higher flow rates tend to maintain the driving force. The fourth process considered is an example of generative flow dependence. In this case the flow-sensitive component of the driving force is generated within the transporting segment. Flow affects the transport process by preventing dissipation of the driving force, as in the first three cases. Both types of processes can be expected to be more flow dependent in some lower range of flow rate and to be less flow dependent in some higher range of flow rate. This is because the proximate cause of a change in transport, a flow-dependent change in driving force is larger for a given change of flow rate when flow rates are relatively slow.

Intracellular H+ regulates the α-subunit of ENaC, the epithelial Na+ channel

1999 ◽  
Vol 276 (2) ◽  
pp. C477-C486 ◽  
Author(s):  
Michael L. Chalfant ◽  
Jerod S. Denton ◽  
Bakhram K. Berdiev ◽  
Iskander I. Ismailov ◽  
Dale J. Benos ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Molecular Mechanisms ◽  
Single Channel ◽  
Collecting Duct ◽  
Regulatory Protein ◽  
Sodium Absorption ◽  
Na Channel ◽  
Open Probability ◽  
Α Subunit ◽  
Effect Of Ph

Protons regulate electrogenic sodium absorption in a variety of epithelia, including the cortical collecting duct, frog skin, and urinary bladder. Recently, three subunits (α, β, γ) coding for the epithelial sodium channel (ENaC) were cloned. However, it is not known whether pH regulates Na+ channels directly by interacting with one of the three ENaC subunits or indirectly by interacting with a regulatory protein. As a first step to identifying the molecular mechanisms of proton-mediated regulation of apical membrane Na+ permeability in epithelia, we examined the effect of pH on the biophysical properties of ENaC. To this end, we expressed various combinations of α-, β-, and γ-subunits of ENaC in Xenopusoocytes and studied ENaC currents by the two-electrode voltage-clamp and patch-clamp techniques. In addition, the effect of pH on the α-ENaC subunit was examined in planar lipid bilayers. We report that α,β,γ-ENaC currents were regulated by changes in intracellular pH (pHi) but not by changes in extracellular pH (pHo). Acidification reduced and alkalization increased channel activity by a voltage-independent mechanism. Moreover, a reduction of pHi reduced single-channel open probability, reduced single-channel open time, and increased single-channel closed time without altering single-channel conductance. Acidification of the cytoplasmic solution also inhibited α,β-ENaC, α,γ-ENaC, and α-ENaC currents. We conclude that pHi but not pHo regulates ENaC and that the α-ENaC subunit is regulated directly by pHi.

scholarly journals Modeling of a controlled flow cup for improved transitional drinking development in children

2021 ◽  
Vol 8 ◽  
pp. 205566832110087
Author(s):  
Michael M Bailey-Van Kuren ◽  
Donna Scarborough
Keyword(s):  
Flow Rate ◽  
Volumetric Flow Rate ◽  
Swallowing Disorders ◽  
Design Tool ◽  
Liquid Volume ◽  
System Control ◽  
Flow Rates ◽  
Controlled Flow ◽  
Fast Flow ◽  
Cup Design

Introduction Clinical observations of children with swallowing disorders using a traditional “sippy” or transitional drinking cup identified a need for a novel cup. Children with swallowing disorders are often unable to initiate the forces required to activate the cup and/or maintain suction pressure. Furthermore, fast flow rates can result in choking. Methods A new cup design tool is proposed using fluid-cup interactions to capture the changing geometry of the fluid during drinking. A Petri net formulation is integrated with standard fluid flow principles. A new parametric cup simulation provides visualization and direct implementation for microcontroller prototypes. A vent-based controller is developed and modeled for a novel transitional drinking cup design. A simulated pouring study is performed for water and a baseline liquid volume of 200 ml in the cup. The study varies rotation rates, initial volume, system control and desired flow rates. Results Volumetric flow rate curves over time are generated and compared in relation to a target flow rate. The simulation results show expected behavior for variations in cup parameters. Conclusion The new simulation model facilitates future dysphagia research through rapid prototyping by tuning cup geometry, liquid parameters and control signals to meet the varying needs of the users.

scholarly journals Hyperfiltration and inner stripe hypertrophy may explain findings by Gamble and coworkers

2010 ◽  
Vol 298 (4) ◽  
pp. F962-F972 ◽  
Author(s):  
Anita T. Layton ◽  
Thomas L. Pannabecker ◽  
William H. Dantzler ◽  
Harold E. Layton
Keyword(s):  
Mathematical Model ◽  
Boundary Conditions ◽  
Transport Properties ◽  
Flow Rate ◽  
Collecting Duct ◽  
Urine Osmolality ◽  
Urine Flow ◽  
Supplemental Feeding ◽  
Duct System ◽  
Flow Rates

Simulations conducted in a mathematical model were used to exemplify the hypothesis that elevated solute concentrations and tubular flows at the boundary of the renal outer and inner medullas of rats may contribute to increased urine osmolalities and urine flow rates. Such elevated quantities at that boundary may arise from hyperfiltration and from inner stripe hypertrophy, which are correlated with increased concentrating activity (Bankir L, Kriz W. Kidney Int. 47: 7–24, 1995). The simulations used the region-based model for the rat inner medulla that was presented in the companion study (Layton AT, Pannabecker TL, Dantzler WH, Layton HE. Am J Physiol Renal Physiol 298: F000–F000, 2010). The simulations were suggested by experiments which were conducted in rat by Gamble et al. (Gamble JL, McKhann CF, Butler AM, Tuthill E. Am J Physiol 109: 139–154, 1934) in which the ratio of NaCl to urea in the diet was systematically varied in eight successive 5-day intervals. The simulations predict that changes in boundary conditions at the boundary of the outer and inner medulla, accompanied by plausible modifications in transport properties of the collecting duct system, can significantly increase urine osmolality and flow rate. This hyperfiltration-hypertrophy hypothesis may explain the finding by Gamble et al. that the maximum urine osmolality attained from supplemental feeding of urea and NaCl in the eight intervals depends on NaCl being the initial predominant solute and on urea being the final predominant solute, because urea in sufficient quantity appears to stimulate concentrating activity. More generally, the hypothesis suggests that high osmolalities and urine flow rates may depend, in large part, on adaptive modifications of cortical hemodynamics and on outer medullary structure and not entirely on an extraordinary concentrating capability that is intrinsic to the inner medulla.

Hydraulic model of a water cooling system in a chemical plant

1988 ◽  
Vol 53 (4) ◽  
pp. 788-806
Author(s):  
Miloslav Hošťálek ◽  
Jiří Výborný ◽  
František Madron
Keyword(s):  
Flow Rate ◽  
Cooling System ◽  
Cooling Water ◽  
Graph Algorithm ◽  
Automatic Generation ◽  
Hydraulic Calculation ◽  
Return Flow ◽  
Flow Rates ◽  
Pressure Losses ◽  
Controlled Flow

Steady state hydraulic calculation has been described of an extensive pipeline network based on a new graph algorithm for setting up and decomposition of balance equations of the model. The parameters of the model are characteristics of individual sections of the network (pumps, pipes, and heat exchangers with armatures). In case of sections with controlled flow rate (variable characteristic), or sections with measured flow rate, the flow rates are direct inputs. The interactions of the network with the surroundings are accounted for by appropriate sources and sinks of individual nodes. The result of the calculation is the knowledge of all flow rates and pressure losses in the network. Automatic generation of the model equations utilizes an efficient (vector) fixing of the network topology and predominantly logical, not numerical operations based on the graph theory. The calculation proper utilizes a modification of the model by the method of linearization of characteristics, while the properties of the modified set of equations permit further decrease of the requirements on the computer. The described approach is suitable for the solution of practical problems even on lower category personal computers. The calculations are illustrated on an example of a simple network with uncontrolled and controlled flow rates of cooling water while one of the sections of the network is also a gravitational return flow of the cooling water.

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