PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “OSMOSIS AND PERMEABILITY”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources

Effects of PCMBS on the water and small solute permeabilities in frog urinary bladder.

UNLABELLED: It has been reported that PCMBS (p-chloromercuribenzene sulfonate) blocks the water permeability of red cells and of the tubular kidney membranes. In this study we compare the effects of this mercurial compound on the permeability of water and other small solutes in the frog urinary bladder. We observed that: (i) 5 mM PCMBS applied at pH 5.0 to the mucosal side inhibited the net and unidirectional water fluxes induced by oxytocin without changing the delta Pf/delta Pd ratio. (ii) The oxytocin-induced urea and Na+ influxes were also inhibited by PCMBS. (iii) The unidirectional Cl- movement was first reduced and then increased during the course of PCMBS treatment. (iv) The short-circuit measured at low mucosal Na+ concentration (10 mM), diminished continuously, whereas the transepithelial resistance first increased and then diminished. (v) Mannitol, raffinose, alpha-methyl-glucose, antipyrine, caffeine and Rb+ movements were not changed significantly during the first 26 min of the water permeability inhibition. IN CONCLUSION: (i) The ADH-sensitive water, urea and Na+ transport systems were inhibited by PCMBS, (ii) PCMBS did not induce a nonspecific and general effect on the permeability of the membrane during the development of the water permeability inhibition, and (iii) in terms of water channels, the inhibition of water transport with the maintenance of a high Pf/Pd ratio suggests that PCMBS closes the water channels in an all or none manner, reducing their operative number in the apical border of frog bladder.

4-Chloromercuribenzenesulfonate↗

Synthesis and characterization of 2-nitro-5-aziodobenzoylglycyloxytocin, an oxytocin photoaffinity label.

The oxytocin analogue, 2-nitro-5-azidobenzoylglycyloxytocin (NAB-Gly-oxytocin), has been synthesized and purified. The analogue is a full agonist for the stimulation of osmotic water flow in the toad urinary bladder (one-half maximal activity at 3.2 X 10(-6)M). It also enhances [14C]urea permeability in this tissue. Repetitive photolysis in the presence of NAB-Gly-oxytocin (8 X 10(-6)M) results in a progressive permanent inhibition of oxytocin stimulated urea permeability but does not alter hormone induced 3H2O movement. The inhibition is dependent on the photogeneration of the aryl nitrene intermediate and is relieved by protecting the hormone receptor with excess oxytocin (10(-6)M) during the photolysis. These results suggest that the photodependent permanent inhibition of the response to oxytocin in the toad bladder is due to covalent incorporation of the photoaffinity label, NAB-Gly-oxytocin, into the hormone receptor.

Affinity Labels↗

The single file hypothesis and the water channels induced by antidiuretic hormone.

Unidirectional and net water movements were determined at minute intervals in frog urinary bladders. The changes in both parameters were followed, during the action of antidiuretic hormone (ADH), at different temperatures and stirring conditions. After correction for external unstirred layer effects, the ratio of the osmotic (Pf) and diffusional (Pd) permeability coefficients was remarkably constant, at different times and in different experimental conditions. In the presence of ADH the delta Pf/delta Pd ratio in the mucosal border was probably greater than 9. On the other hand, in nonstimulated preparations the ratio was smaller, and probably not different from 1. These results, together with previous observations indicating that other small molecules (like urea) are excluded from the ADH-induced channel, might indicate that single-file water movement can occur through this structure. Alternatively, the delta Pf/delta Pd ratio could result from a complex geometric arrangement in series with the aqueous pore.

Animals↗

A component of fluid absorption linked to passive ion flows in the superficial pars recta.

We studied salt and water absorption in isolated rabbit superficial proximal straight tubules perfused and bathed with solutions providing oppositely directed transepithelial anion gradients similar to those which might obtain in vivo. The perfusing solution contained 138.6 mM Cl- 3.8 mM HCO-3 (pH 6.6) while the bathing solution contained 113.6 mM Cl- and 25 mM HCO-3 (pH 7.4); the system was bubbled with 95% O2-5% CO2. At 37 degrees C, net volume absorption (Jv nl min-1 mm-1) was 0.32 +/- 0.03 (SEM); Ve, the transepithelial voltage (millivolts; lumen to bath), was +3.1 +/- 0.2. At 21 degrees C, Ve rose to +3.7 +/- 0.1 and Jv fell to 0.13 +/- 0.01 (significantly different from zero at P less than 0.001); in the presence of 10(-4)M ouabain at 37 degrees C, Ve rose to +3.8 +/- 0.1 and Jv fell to 0.16 +/- 0.01 (P less than 0.001 with respect to zero). In paired experiments, the ouabain- and temperature-insensitive moieties of Jv and Ve became zero when transepithelial anion concentration gradients were abolished. Titrametric determinations net chloride flux at 21 degrees C or at 37 degrees C with 10(-4) M ouabain showed that chloride was the sole anion in an isotonic absorbate. And, combined electrical and tracer flux data indicated that the tubular epithelium was approximately 18 times more permeable to Cl- than to HCO-3. We interpret these results to indicate that, in these tubules, NaCl absorption depends in part on transepithelial anion concentration gradients similar to those generated in vivo and in vitro by active Na+ absorption associated with absorption to anions other than chloride. A quantitative analysis of passive solute and solvent flows in lateral intercellular spaces indicated that fluid absorption occurred across junctional complexes when the osmolality of the lateral intercellular spaces was equal to or slightly less than that of the perfusing and bathing solutions; the driving force for volume flow under these conditions depended on the fact that sigmaHCO3 exceeded sigmaCl.

Absorption↗

Experimental tests of three-dimensional model of urinary concentrating mechanism.

Recently, a new model of the urinary concentrating process has been proposed that takes into account the three-dimensional architecture of the renal medulla. Under the assumptions of the model, computer simulations predicted significant axial osmolality gradients in the inner medulla without active transport by the inner medullary loop of Henle. Two of the model assumptions (which constitute hypotheses for this study) were: (1) the osmotic water permeability of the initial part of the inner medullary collecting duct (initial IMCD) is very low even in the presence of vasopressin; and (2) there is significant lateral separation of structures such that thin descending limbs are far from the collecting ducts at the same inner medullary level. The first hypothesis was addressed by perfusing rat initial IMCD segments in vitro and measuring osmotic water permeability. With the osmotic gradient oriented as predicted by the model (lumen greater than bath), vasopressin increased the osmotic water permeability from 286 to 852 microns/s. Three additional series of experiments confirmed the high water permeability in the presence of vasopressin. The second hypothesis was addressed by morphometric analysis of histologic cross-sections of the rat renal medulla. Mean distances of descending limbs to the nearest adjacent collecting duct were very small throughout the inner medulla (less than 6 microns) and substantially less than in the outer medulla (28 microns). It was concluded that the data are inconsistent with both hypotheses and therefore do not support the feasibility of the "three-dimensional" model of the renal inner medulla. The axial distributions of loops of Henle and collecting ducts in the rat renal medulla are also reported.

Animals↗

The inner mitochondrial membrane has aquaporin-8 water channels and is highly permeable to water.

Mitochondria are remarkably plastic organelles constantly changing their shape to fulfil their various functional activities. Although the osmotic movement of water into and out of the mitochondrion is central for its morphology and activity, the molecular mechanisms and the pathways for water transport across the inner mitochondrial membrane (IMM), the main barrier for molecules moving into and out of the organelle, are completely unknown. Here, we show the presence of a member of the aquaporin family of water channels, AQP8, and demonstrate the strikingly high water permeability (Pf) characterizing the rat liver IMM. Immunoblotting, electron microscopy, and biophysical studies show that the largest mitochondria feature the highest AQP8 expression and IMM Pf. AQP8 was also found in the mitochondria of other organs, whereas no other known aquaporins were seen. The osmotic water transport of liver IMM was partially inhibited by the aquaporin blocker Hg2+, while the related activation energy remained low, suggesting the presence of a Hg2+-insensitive facilitated pathway in addition to AQP8. It is suggested that AQP8-mediated water transport may be particularly important for rapid expansions of mitochondrial volume such as those occurring during active oxidative phosphorylation and those following apoptotic signals.

Animals↗

Diluting segment in kidney of dogfish shark. I. Localization and characterization of chloride absorption.

Single tubules, dissected from the peritubular sheath of the dorsal bundle zone of kidney of the dogfish shark, Squalus acanthias, were perfused in vitro at 17-18 degrees C. This segment is the largest of the five in the peritubular sheath and had average inner and outer diameters of 46.9 +/- 1.2 and 74.4 +/- 2.1 microns, respectively (n = 32). These values suggest that this is the intermediate IV segment. When perfused with symmetrical buffered elasmobranch saline, intermediate IV segments exhibited high rates of Cl- absorption (JCl, pmol.s-1.cm-2): 1,696 at an average perfusion rate (Vo) of 8.2 nl/min. Cl- absorption was highly flow dependent [1/JCl = 57.95(1/Vo) + 1.75; r = 0.71, P less than 0.01]. Maximal rates of Cl-absorption, calculated from reciprocal transformation of the flow dependence of JCl, yielded a value of 5,714 pmol.s-1.cm-2. In the presence of a 200-mosmol/kg transepithelial osmotic gradient, fluid absorption was negligible. The spontaneous transepithelial voltage (Vte, mucosal with respect to serosal compartment) averaged 8.0 +/- 1.0 mV (n = 26). Such active transport of Cl- in the absence of fluid movement and in the presence of a lumen-positive transepithelial voltage is characteristic of amphibian and mammalian diluting segments. Na(+)-to-Cl- permeability ratios (PNa/PCl) averaged 2.5 +/- 0.5, indicating that, as in mammalian thick ascending limbs, this segment is Na+ (cation) permselective. Vte was dependent on the presence of Na+ and Cl- in the external solutions and was reversibly abolished by isosmotic replacement with N-methyl-D-glucamine or with isethionate, respectively. Ouabain inhibited Vte but was not reversible within the time course of these experiments. Furosemide (10(-4) M), but not equimolar concentrations of amiloride or hydrochlorothiazide, added to the luminal perfusate inhibited both Vte and JCl. These results suggest that apical membrane Na+ entry in intermediate IV segments is mediated by Na(+)-K(+)-Cl- cotransport and is consistent with the existence of a functional role of urinary dilution in the reabsorption of urea in the elasmobranch kidney.

Absorption↗

ADH-induced water permeability and particle aggregates: alteration by a synthetic estrogen.

In the amphibian urinary bladder, the increase in water permeability induced by antidiuretic hormone (ADH) is accompanied by the appearance of apical intramembrane particle (IMP) aggregates that are believed to contain specific channels for water. In a previous work, we have shown that 3,3'-diallyldiethylstilbestrol (DADES), a synthetic estrogen which is a blocker of the glucose transporter, also inhibits the hydrosmotic response to ADH in the bladder. Our aim in the present study was to analyze the alterations of the membrane fine structure further and to correlate them with the water permeability changes. The results point to a selective inhibition of the ADH-induced net water flow, probably due to an interference with one of the last steps of the response to the hormone. This inhibition is associated with an increase in the density of the apical IMP aggregates, which are thus probably not operational. The resting net water flow is not inhibited and, surprisingly, typical IMP aggregates are frequently observed in the apical membrane after DADES treatment. The compound also induces the appearance of unusual loose IMP clusters that can only be seen on the apical membrane of the granular cells and that share several ultrastructural similarities with the ADH-induced aggregates. These results suggest that 1) apical DADES treatment stimulates the insertion of IMP aggregates in the apical membrane of the urinary bladder and 2) DADES inhibits the ADH-induced water flow by interfering with the aggregates and thus probably by blocking the specific water channels.

Animals↗

Osmotic work across inner medullary collecting duct accomplished by difference in reflection coefficients for urea and NaCl.

To demonstrate that osmotic work can be accomplished across the inner medullary collecting duct (IMCD) by the difference in reflection coefficients for urea and NaCl, phenomenological coefficients for urea and NaCl transport were determined in isolated segments of the hamster IMCD perfused in vitro. Arginine vasopressin at 100 microU/ml increased urea permeability from 11.5 +/- 2.9 to 31.7 +/- 4.2 x 10(-7) cm2 s-1 in the middle IMCD but not in the upper IMCD. Urea transport in the middle IMCD consisted of two components, transport with saturable kinetics and simple passive diffusion. Permeability to Na+ was very low (2 x 10(-7) cm2 s-1). Reflection coefficients as measured by the equiosmolality method, with raffinose being a reference solute, were 0.87 +/- 0.05 and 0.71 +/- 0.04 for urea and 1.03 +/- 0.07 and 0.91 +/- 0.04 for NaCl in the upper and the middle IMCD, respectively. Reflection coefficient for urea in the middle IMCD was 0.68 when determined by the zero volume flux method. When the middle IMCD was perfused with bicarbonate Krebs-Ringer (BKR) solution containing 200 mmol/l urea, the replacement of urea in the bathing fluid with equisomolal NaCl caused large volume flux (3.81 +/- 0.45 nl mm-1 min-1) associated with dilatation of intercellular space. The existence of vasopressin in the bath was essential for this phenomenon. This effect was inhibited by 5 x 10(-4) M phloretin in the bath, suggesting that the vasoressin-stimulated urea transport is responsible for this phenomenon. From these observations, we conclude that transport parameters of the middle IMCD are appropriate for accomplishment of osmotic work across this segment in the absence of physicochemical osmotic gradients.

Animals↗

Reduced osmotic water permeability of the peritoneal barrier in aquaporin-1 knockout mice.

Aquaporin-1 (AQP1) water channels are expressed widely in epithelia and capillary endothelia involved in fluid transport. To test whether AQP1 facilitates water movement from capillaries into the peritoneal cavity, osmotically induced water transport rates were compared in AQP1 knockout [(-/-)], heterozygous [(+/-)], and wild-type [(+/+)] mice. In (+/+) mice, RT-PCR showed detectable transcripts for AQP1, AQP3, AQP4, AQP7, and AQP8. Immunofluorescence showed AQP1 protein in capillary endothelia and mesangium near the peritoneal surface and AQP4 in adherent muscle plasmalemma. For measurement of water transport, 2 ml of saline containing 300 mM sucrose (600 mosM) were infused rapidly into the peritoneal cavity via a catheter. Serial fluid samples (50 microliter) were withdrawn over 60 min, with albumin as a volume marker. The albumin dilution data showed significantly decreased initial volume influx in AQP1 (-/-) mice: 101 +/- 8, 107 +/- 5, and 42 +/- 4 (SE) microliter/min in (+/+), (+/-), and (-/-) mice, respectively [n = 6-10, P < 0.001, (-/-) vs. others]. Volume influx for AQP4 knockout mice was 100 +/- 8 microliters/min. In the absence of an osmotic gradient, 3H2O uptake [half time = 2.3 and 2.2 min in (+/+) and (-/-) mice, respectively], [14C]urea uptake [half time = 7.9 and 7.7 min in (+/+) and (-/-) mice, respectively], and spontaneous isosmolar fluid absorption from the peritoneal cavity [0.47 +/- 0.05 and 0.46 +/- 0.04 ml/h in (+/+) and (-/-) mice, respectively] were not affected by AQP1 deletion. Therefore, AQP1 provides a major route for osmotically driven water transport across the peritoneal barrier in peritoneal dialysis.

Animals↗

Prostaglandin E2 activates outwardly rectifying Cl(-) channels via a cAMP-dependent pathway and reduces cell motility in rat osteoclasts.

We examined changes in electrical and morphological properties of rat osteoclasts in response to prostaglandin (PG)E(2). PGE(2) (>10 nM) stimulated an outwardly rectifying Cl(-) current in a concentration-dependent manner and caused a long-lasting depolarization of cell membrane. This PGE(2)-induced Cl(-) current was reversibly inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), and tamoxifen. The anion permeability sequence of this current was I(-) > Br(-) approximately Cl(-) > gluconate(-). When outwardly rectifying Cl(-) current was induced by hyposmotic extracellular solution, no further stimulatory effect of PGE(2) was seen. Forskolin and dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) mimicked the effect of PGE(2). The PGE(2)-induced Cl(-) current was inhibited by pretreatment with guanosine 5'-O-2-(thiodiphosphate) (GDPbetaS), Rp-adenosine 3',5'-cyclic monophosphorothioate (Rp-cAMPS), N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide dihydrochloride (H-89), and protein kinase A inhibitors. Even in the absence of nonosteoclastic cells, PGE(2) (1 microM) reduced cell surface area and suppressed motility of osteoclasts, and these effects were abolished by Rp-cAMPS or H-89. PGE(2) is known to exert its effects through four subtypes of PGE receptors (EP1-EP4). EP2 and EP4 agonists (ONO-AE1-259 and ONO-AE1-329, respectively), but not EP1 and EP3 agonists (ONO-DI-004 and ONO-AE-248, respectively), mimicked the electrical and morphological actions of PGE(2) on osteoclasts. Our results show that PGE(2) stimulates rat osteoclast Cl(-) current by activation of a cAMP-dependent pathway through EP2 and, to a lesser degree, EP4 receptors and reduces osteoclast motility. This effect is likely to reduce bone resorption.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Water permeability and its activation energy for individual hamster pancreatic islet cells.

Coupled with the rapid development of clinical pancreatic islet transplantation, there is an increasing requirement for cryopreservation of viable islets. Fundamental cryobiology requires determination of several cryobiophysical parameters to predict optimal cryopreservation procedures. These include water permeability or hydraulic conductivity (Lp) and its activation energy (Ea), the permeability of the cell plasma membrane to a cryoprotectant(s) (Ps) and its Ea, the osmotically inactive fraction of cell volume (Vb), and the intracellular ice formation temperature. For islet cells, these parameters have not previously been reported. In the present studies, the Lp, its Ea, and Vb were determined for isolated individual golden hamster pancreatic islet cells. The Lp and Vb parameters were also measured for corresponding exocrine cells. Both islet and the exocrine cells appeared to be ideal osmometers over the experimental range when examined by the Boyle Van't-Hoff relationship (linear regression, r = 0.99 for both types of cells). Extrapolation of these plots generated Vb values of 0.40 for the islet cells and 0.45 for the pancreatic exocrine cells. To determine the Lp, kinetic changes of cell volume over time (dv/dt) in response to anisoosmotic conditions (ranging from 145 mOsm/kg to 1.35 Osm/kg) were measured using an electronic particle counter. The experimental data were fitted to generate the Lp values by least-squares curve fitting to a differential equation describing osmotic water movement across the plasma membrane. For pancreatic islet cells, the Lp was determined to be 0.25 +/- 0.03 microns/min/atm (mean +/- SD, n = 14) at 22 degrees C, 0.54 +/- 0.07 (n = 10), 0.06 +/- 0.008 (n = 9), and 0.01 +/- 0.001 (n = 9) at 37, 8 and 0 degrees C, respectively. The Ea for Lp was calculated from the slope of the Arrhenius plot based upon the mean Lp values at the four different temperatures. The Ea was 16.21 Kcal/mol between 0 and 37 degrees C. Based upon these values, an optimal cooling rate for cryopreserving pancreatic islet cells is predicted to be approximately 0.5 degrees C min. The Lp for the individual exocrine cells was determined to be 3.73 +/- 1.75 microns/min/atm (n = 13) at 22 degrees C, which was approximately 10 times the Lp value of the corresponding islet cells.

Animals↗

Sarcolemmal hydraulic conductivity of guinea-pig and rat ventricular myocytes.

OBJECTIVE: Osmotic gradient-induced volume change and sarcolemmal water permeability of cardiac myocytes were evaluated to characterize the mechanism of water flux across the plasma membranes. METHODS: Cell surface dimensions were measured from isolated guinea-pig and rat ventricular myocytes by digital videomicroscopy, and membrane hydraulic conductivity (L(p)) was obtained by analyzing the time course of cell swelling and shrinkage in response to osmotic gradients. RESULTS: Superfusion with anisosmotic solution (0.5-4 times normal osmolality) caused a rapid (<3 min to steady states) and reversible myocyte swelling or shrinkage. L(p) was approximately 1.9 x 10(-10) l N(-1) s(-1) for guinea-pig myocytes and approximately 1.7 x 10(-10) l N(-1) s(-1) for rat myocytes at 35 degrees C. Arrhenius activation energy (E(a)), a measure of the energy barrier to water flux, was approximately 3.7 (guinea-pig) and approximately 3.6 kcal mol(-1) (rat) between 11 and 35 degrees C; these values are equivalent to E(a) of self-diffusion of water in bulk solution ( approximately 4 kcal mol(-1)). Treatment with 0.1 mM Hg(2+), a sulfhydryl-oxidizing reagent that blocks membrane water channels, reduced L(p) by approximately 80%, and the sulfhydryl-reducing reagent dithiothreitol (10 mM) antagonized the inhibitory action of Hg(2+). Inhibition of the volume-sensitive cation (30 microM Gd3+) and anion (1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonate) channels and Na+-K+ pump (10 microM ouabain) modified the size of osmotic swelling but had little effect on L(p). CONCLUSIONS: Although the observed L(p) is relatively small in magnitude, the low E(a) and the sulfhydryl reagent-induced modification of L(p) are characteristic of channel-mediated water transport. These data suggest that water flux across the sarcolemma of guinea-pig and rat heart cells occurs through parallel pathways, i.e., the majority passing through water channels and the remainder penetrating the lipid bilayers.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Osmotic properties of Ehrlich ascites tumor cells during the cell cycle.

Ehrlich ascites tumor cells were grown and maintained in continuous spinner culture. The population of dividing cells was synchronized by a double thymidine block technique. Cell cycle phases were determined graphically by plotting mitotic index, cell number, and DNA synthesis against time. Changes in the osmotic properties of Ehrlich ascites tumor cells during the cell cycle are described. Permeability to water is highest at the initiation of S and progressively decreases to its lowest value just after mitosis. Heats of activation for water permeability vary during the cell cycle, ranging from 9-14 kcal/mole. Results may imply changes in the state of water in the membrane during the cycle. The volume of osmotically active cell water is highest during S and early G2 and decreases during the mitotic phase, as cells undergo division. Total water content remains stable at 82% (w/w) during the cycle. Total concentration of the three major ions (Na, K, Cl), expressed as mEq/liter total cell volume, does not change. The fraction of total cell water which is osmotically active (Ponder's R) decreased gradually from 0.75 at S to about 0.56 following mitosis. Findings suggest that a fraction of the total water within the cell exists in a "bound" form and is, therefore, incapable of being shifted under the driving force of osmotic pressure. This fraction of bound water increases during the cell cycle. Possible alterations in membrane fluidity and the state of water in the cell are discussed.

Animals↗

Impaired hydroosmotic response to vasopressin of cortical collecting tubules from lithium-treated rabbits.

The hydroosmotic action of [arginine]vasopressin (vasopressin, 25 microU/ml) and of 8-Br-cAMP (10(-4)M) was studied in vitro in perfused cortical collecting tubules (CCT) isolated from rabbits fed with lithium chloride for 3 weeks. Vasopressin-dependent water reabsorption was significantly inhibited by 65% although no lithium was used in the in vitro experiments. The hydroosmotic action of 8-Br-cAMP was also inhibited by previous Li treatment, but the effect was smaller in magnitude. Water intake, diuresis, and urinary osmolality were no different in the lithium-treated animals as compared with respective pretreatment values or with control animals given an equivalent amount of sodium chloride. Neither the creatinine clearance nor the maximal urinary concentrating ability were modified by lithium treatment. A mathematical model simulating water reabsorption along the CCT predicts that a 65% reduction of vasopressin-stimulated hydraulic conductivity, as observed in the Li group, may not be sufficient to prevent a complete osmotic equilibration at the end of the CCT in vivo. We conclude that: (a) in the rabbit, lithium administration induces an impairment of the hydroosmotic action of vasopressin in the CCT, which is due to an inhibition of pre- and post-cAMP events. (b) The inhibition of vasopressin action can be demonstrated in vitro at a time when no detectable impairment of the water conservation process occurs in vivo.

8-Bromo Cyclic Adenosine Monophosphate↗

A mathematical model of electrolyte and fluid transport across corneal endothelium.

To predict the behavior of a transporting epithelium by intuitive means can be complex and frustrating. As the number of parameters to be considered increases beyond a few, the task can be termed impossible. The alternative is to model epithelial behavior by mathematical means. For that to be feasible, it has been presumed that a large amount of experimental information is required, so as to be able to use known values for the majority of kinetic parameters. However, in the present case, we are modeling corneal endothelial behavior beginning with experimental values for only five of eleven parameters. The remaining parameter values are calculated assuming cellular steady state and using algebraic software. With that as base, as in preceding treatments but with a distribution of channels/transporters suited to the endothelium, temporal cell and tissue behavior are computed by a program written in Basic that monitors changes in chemical and electrical driving forces across cell membranes and the paracellular pathway. We find that the program reproduces quite well the behaviors experimentally observed for the translayer electrical potential difference and rate of fluid transport, (a) in the steady state, (b) after perturbations by changes in ambient conditions HCO3-, Na+, and Cl- concentrations), and (c) after challenge by inhibitors (ouabain, DIDS, Na+- and Cl(-)-channel inhibitors). In addition, we have used the program to compare predictions of translayer fluid transport by two competing theories, electro-osmosis and local osmosis. Only predictions using electro-osmosis fit all the experimental data.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗