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Biomedical subjects

W Nagel

Publications and source records attributed to W Nagel.

At least 91 records · Page 5Linked to original sources
PubMed1987

Origin of transport inhibition after omission of serosal sodium.

The omission of sodium from the serosal incubation fluid in isolated frog skins inhibits transcellular Na transport. By the use of intracellular recording with microelectrodes, it has been demonstrated that this inhibition is associated with an increase of the basolateral membrane resistance, resulting in a depolarization of the short-circuited cells. This depolarization in turn accounts for the reduction of Na entry across the apical border. The resistance changes across the outer (apical) border are small in magnitude and unrelated to the inhibition of transcellular transport. The origin of the increase in basolateral membrane resistance, presumably due to decrease of K permeability, is unclear. These data do not support the hypothesis that intracellular Ca regulates the resistance of the apical and basolateral membranes.

Animals↗
PubMed1986

Basolateral membrane potential and conductance in frog skin exposed to high serosal potassium.

In studies of apical membrane current-voltage relationships, in order to avoid laborious intracellular microelectrode techniques, tight epithelia are commonly exposed to high serosal K concentrations. This approach depends on the assumptions that high serosal K reduces the basolateral membrane resistance and potential to insignificantly low levels, so that transepithelial values can be attributed to the apical membrane. We have here examined the validity of these assumptions in frog skins (Rana pipiens pipiens). The skins were equilibrated in NaCl Ringer's solutions, with transepithelial voltage Vt clamped (except for brief perturbations delta Vt) at zero. The skins were impaled from the outer surface with 1.5 M KCl-filled microelectrodes (Rel greater than 30 M omega). The transepithelial (short-circuit) current It and conductance gt = -delta It/delta Vt, the outer membrane voltage Vo (apical reference) and voltage-divider ratio (Fo = delta Vo/delta Vt), and the microelectrode resistance Rel were recorded continuously. Intermittent brief apical exposure to 20 microM amiloride permitted estimation of cellular (c) and paracellular (p) currents and conductances. The basolateral (inner) membrane conductance was estimated by two independent means: either from values of gt and Fo before and after amiloride or as the ratio of changes (-delta Ic/delta Vi) induced by amiloride. On serosal substitution of Na by K, within about 10 min, Ic declined and gt increased markedly, mainly as a consequence of increase in gp. The basolateral membrane voltage Vi (= -Vo) was depolarized from 75 +/- 4 to 2 +/- 1 mV [mean +/- SEM (n = 6)], and was partially repolarized following amiloride to 5 +/- 2 mV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Evidence for separate cellular origins of sodium and acid-base transport in the turtle bladder.

Transmembrane electrical parameters of the epithelial cells in short-circuited turtle bladders were measured to determine whether those cells participating in Na reabsorption also participate in electrogenic transepithelial acidification and alkalinization. Amiloride-induced increases in intracellular potential (Vsca), apical fractional resistance (FRa), and concomitant decreases in short-circuit current (Isc) denote the participation of the impaled cells in Na reabsorption. In bladders from postabsorptive turtles, amiloride increased Vsca by -45 mV, increased FRa by 37%, and decreased Isc from 36 to -10 microA/cm2. In bladders from NaHCO3-loaded turtles, amiloride increased Vsca by -21 mV, FRa by 21%, and decreased Isc from 22 to 0 microA/cm2. Neither the subsequent inhibition of the negative acidification current in postabsorptive bladders, nor stimulation of positive alkalinization current in bladders from NaHCO3-loaded turtles was associated with any transmembrane electrical change that could be attributed to changes in those transport processes. It is concluded that the electrogenic luminal acidification and alkalinization processes of the turtle bladder are not produced by, or electrically coupled to, those cells that are involved in Na reabsorption.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Basolateral membrane ionic conductance in frog skin.

The basolateral membrane resistance of frog skin was determined using standard equivalent circuit analysis. Data obtained with different formal approaches were found to deviate sometimes drastically; however, the data do not permit to identify the origin of this inconsistency nor do they indicate which kind of equivalent circuit calculation yields inappropriate results. Within either formulation, response to experimental perturbation appears to be qualitatively accessible. Using increasing concentrations of amiloride to inhibit transcellular current flow, I/V relationships of the basolateral membrane were obtained which showed pronounced non-linearity with decreasing resistance at decreasing current (and hyperpolarizing membrane). The shape of the I/V relationship was opposite after serosal Ba2+. It is suggested that the potassium channels of the basolateral membrane might show kind of inward or "anomalous" rectification known from other membranes.

Amiloride↗
PubMed1985

Opposite effects of indacrinone (MK-196) on sodium and chloride conductance of amphibian skin.

Indacrinone, a drug chemically related to ethacrynic acid, usually stimulated reversibly short circuit current and sodium influx when applied to the epithelial surface of amphibian skin. Concomitantly, transepithelial conductance, gt, decreased, provided chloride was the main anion in the incubation fluid. Electrophysiological analysis including microelectrode impalement indicated that the drug increased the sodium-conductance at the apical border of the impaled (most likely granular) cells. The decrease in gt thus points at shunt conductance being reduced with indacrinone, sometimes drastically. Decrease of transepithelial chloride flux with the drug as well as lack of effect of the drug on gt in the absence of chloride on the epithelial side demonstrate the influence of indacrinone on a chloride specific pathway. Whether this is along a paracellular route or through a cellular compartment not coupled to granular cells (mitochondria-rich cells?) cannot be decided on the basis of the present data.

Amphibians↗
PubMed1985

Implications of an anomalous intracellular electrical response in bullfrog corneal epithelium.

The ionic dependencies of the transepithelial and intracellular electrical parameters were measured in the isolated frog cornea. In NaCl Ringer's the intracellular potential difference Vsc measured under short-circuit conditions depolarized by nearly the same amount after either increasing the stromal-side KCl concentration from 2.5 to 25 mM or exposure to 2 mM BaCl2 (K+ channel blocker). With Ba2+ the depolarization of the Vsc by 25 mM K+ was reduced to one-quarter of the control change. If the Cl-permselective apical membrane resistance Ro remained unchanged, the relative basolateral membrane resistance Ri, which includes the lateral intercellular space, increased at the most by less than twofold after Ba2+. These effects in conjunction with the depolarization of the Vsc by 62 mV after increasing the stromal-side K+ from 2.5 to 100 mM in Cl-free Ringer's as well as the increase of the apparent ratio of membrane resistances (a = Ro/Ri) from 13 to 32 are all indicative of an appreciable basolateral membrane K+ conductance. This ratio decreased significantly after exposure to either 25 mM K+ or Ba2+. The decline of Ro/Ri with 25 mM K+ appears to be anomalous since this decrease is not consistent with just an increase of basolateral membrane conductance by 25 mM K+, but rather perhaps a larger decrease of Ro than Ri. Also an increase of lateral space resistance may offset the effect of decreasing Ri with 25 mM K+. In contrast, Ro/Ri did transiently increase during voltage clamping of the apical membrane potential difference Vo and exposure to 25 mM K+ on the stromal side.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

[Lysozyme in children with acute and chronic inflammatory intestinal diseases].

Fecal lysozyme excretion was determined in two hundred children and adolescent. In sixty three infants with enteritis due to Rotavirus the fecal lysozyme level was found to be significant higher than in the feces of a group of healthy infants (p less than 0.01). Elevated fecal lysozyme excretion could be detected in patients with untreated Crohn's disease. After treatment with Salazosulfapyridine, Prednisone and elemental diet during six week a significant drop in fecal lysozyme level was observed (p less than 0.01). In eighteen adolescent with Colitis ulcerosa and Crohn's disease the lysozyme level of colonic mucosa was found to be significant higher than a control group (p less than 0.01). The fecal lysozyme excretion can be used as an indicator for the clinical activity of the disease, as a control for therapeutic efficiency and a marker for a relapse.

Adolescent↗
PubMed1983

Estrogen agonistic and antagonistic action of 8 non-steroidal antiestrogens on progestin receptor induction in rat pituitary gland and uterus.

All 8 non-steroidal antiestrogens tested considerably increased progestin receptor concentration in the uterus and, to a lesser extent, in the pituitary of ovariectomized rats. However, the pituitary was more sensitive than the uterus to the estrogen antagonistic action of these compounds, in that monohydroxytamoxifen, LY 117,018, enclomiphene, nitromifen, nafoxidine and trans-tamoxifen completely blocked progestin receptor induction by estradiol benzoate. In these tissues the order of the in vitro binding affinity of antiestrogens to cytoplasmic estrogen receptors was not correlated with either their in vivo estrogen agonistic or antagonistic potency.

Animals↗
PubMed1983

Contribution of junctional conductance to the cellular voltage-divider ratio in frog skins.

It has been suggested that distribution of lateral interspace resistance in association with a highly conductive junction can significantly affect the measurement of outer membrane(o)/epithelial(t) voltage divider ratios (Fo = delta Vo/delta Vt), thereby leading to erroneous inferences regarding the outer membrane fractional resistance [fRo = Ro/Rc = Ro/(Ro + Ri)], where Ro and Ri are the outer and inner cell membrane resistance respectively and Rc is the total cell membrane resistance. We present here experimental evidence for this point of view. During seasons when frog skins were highly permeable to Cl, transepithelial conductance gt often exceeded 2 mS/cm2. High concentrations of external amiloride rapidly blocked cellular transport, but gt initially remained high and Fo remained appreciably less than 1.0. These values of Fo were found here to result from low junctional resistance Rj: increase of Rj, either gradually following the administration of amiloride, or abruptly with external replacement of Cl by other anions, was associated with increase of Fo to near unity, without effect on the membrane potential or significant change in the short-circuit current. Experimental results following amiloride validated a simple equivalent circuit model predicting near-linear increase in Fo with progressive decrease in gt and led to plausible values of Rj and lateral space resistance Rl. The possible influence of the paracellular resistance pattern on the evaluation of cell membrane resistances from voltage divider ratios is discussed.

Abdomen↗
PubMed1983

Voltage-dependent K conductance at the apical membrane of Necturus gallbladder.

The epithelial and cellular effects of clamping the transepithelial potential (Vt, mucosa reference) have been investigated in the Necturus gallbladder. Following initial equilibration at short circuit, tissue conductance gt was 4.1 +/- 1.2 (SD) mS/cm2, the apical potential Va was -76 +/- 8 mV, and the apical fractional voltage on brief voltage perturbation (fa = delta Va/delta Vt, reflecting the ratio of apical membrane to transcellular resistance) was 0.72 +/- 0.11 (21 gallbladders, 34 impalements). On clamping Vt at positive values, Va depolarized and fa decreased; at the same time gt decreased. Clamping Vt at negative values produced converse effects. All of the above changes were related directly to the magnitude of the clamping potential Vt and were reversed on return to the short circuit state. Effects of Vt on fa are not due to changes in the extracellular pathway resistances (which, however, contribute to gt). Furthermore, the effects of Vt on fa were abolished by the mucosal application of TEA or Ba, or acidification of the mucosal solution. Thus, these experiments disclose the presence of a voltage-dependent apical K conductance that increases with apical membrane depolarization. The calculated dose-response curve of TEA inhibition of apical conductance and the values of the apparent dissociation constant were in good agreement with those found for K channels in excitable tissues. Mucosal application of the Ca ionophore A23187 shifted the voltage dependence curve of fa to more negative values of Va without altering its shape. The effect of A23187 suggests a possible role of intracellular Ca in the modulation of the apical K channels.

Animals↗
PubMed1982

Analysis of cellular reaction to glucose of toad skin treated with aldosterone.

Toad skin exposed overnight to aldosterone, was examined by means of microelectrodes before and after addition of glucose to the incubation fluid in 7 instances. Glucose addition led with minutes to epithelial cell hyperpolarization associated with increases of conductances at both cell borders, the increase being twice as large (in relative terms) at the basolateral border as at the apical one. Since glucose had no effect on untreated preparations, these observations represent another argument for aldosterone influencing target cells in a way that is not restricted to increased apical conductance.

Aldosterone↗
PubMed1982

Microelectrode studies of the effect of lanthanum on the electrical potential and resistance of outer and inner cell membranes of isolated frog skin.

Microelectrodes were used to investigate the effect of 0.5 mM mucosal lanthanum (La3+) on the intracellular potential and the resistance of outer and inner isolated frog skin (Rana esculenta) cell membranes. Under short-circuit conditions, the transapical membrane potential Vsco (mean value = -65.4 +/- 3.2 mV, inside negative) hyperpolarized to -108.7 +/- 2.3 mV in control skins, after addition of the sodium blocker amiloride. Current-voltage curves for the outer and inner membranes were constructed from the amiloride-inhibitable current versus the outer membrane potential Vo or the inner membrane potential Vi. The outer, and to a lesser degree the inner, membrane showed a characteristic nonlinearity with two slope resistances. Addition of La3+ to the outer medium increased the short-circuit current to 190% of the control value. Vsco concomitantly changed to -28 +/- 3.5 mV and outer and inner membrane resistances fell, considerably attenuating the nonlinearity seen in control skins. La3+ is suggested to raise the conductance by its effect on the surface potential. A secondary long-term inhibitory effect of La3+ on short-circuit current has been observed. It is ascribed to the penetration of La3+ into the sodium channels.

Animals↗
PubMed1982

Relationship of transepithelial electrical potential to membrane potentials and conductance ratios in frog skin.

Previous studies in anuran epithelia have shown that, after clamping the transepithelial voltage in symmetrical sequences for 4-6 min there is near-constancy of the rate of active Na transport and the associated oxidative metabolism, with a near-linear potential dependence of both. Here we have investigated in frog skin the cellular electrophysiolgical events associated with voltage clamping (Vt = inside-outside potential). Increase and decrease of Vt produced converse effects, related directly to the magnitude of Vt. Hyperpolarization resulted in prompt decrease in inward transepithelial current It and increase in fractional outer membrane resistance fRo (as evaluated from small transient voltage perturbations) and in outer membrane potential Vo. Overshoot of Vo was followed by relaxation to a quasi-steady state in minutes. Changes in fRo were progressive, with half times of some 1-5 sec. Changes in transepithelial slope conductance gt were more variable, usually preventing precise evaluation of the outer and inner cell membrane conductances go and gi. Nevertheless, it was shown that go is related inversely to Vt and Vo. Presuming insensitivity of gi to Vt, the dependence of Go on Vo in the steady state much exceeds that predicted by the constant field equation. Apparent inconsistencies with earlier results of others may be attributable to differences in protocol and the complex dependence of go on Vo and/or cellular-current. In contrast to previous findings in tight epithelia at open circuit, differences in Vt were associated with substantial differences in fRo and inner membrane potential Vi. Hyperpolarization of Vt over ranges commonly employed in studies of active transport ad metabolism appears to increase significantly the electrochemical work per Na ion transported.

Animals↗
PubMed1981

Tizolemide-induced changes of passive transport components across the basolateral membrane of isolated frog skin.

The effect on transepithelial Na transport of tizolemide was investigated in isolated frog skin (Rana temporaria). It was found that tizolemide (2-5 mM, serosal side) decreased transepithelial Na transport (measured as short circuit current and as net sodium flux) within 60 min to 25-40% of the control level resulting from reduction of the unidirectional sodium influx. Intracellular recording with microelectrodes revealed that these changes were associated with depolarization of the intracellular space to less than 40% of the control values (averaging - 71.7 +/- 5.1 mV) which is a consequence of a decrease in conductance of the basolateral border to about 25% of the control values. The conductance of the apical border was only slightly reduced. It is suggested that tizolemide blocks the partial conductance of potassium at the basolateral border which secondarily diminishes transepithelial Na transport due to a decrease of the driving force for apical border Na entry. A certain degree of inhibition of the Na-K-ATPase by tizolemide cannot be excluded. When vasopressin (ADH) was added to frog skin after treatment with tizolemide, the response was markedly reduced compared to that of untreated control preparations. Under these conditions, the conductance of the basolateral border increased while the apical border remained little influenced by the hormone--opposite to the response of frog skins under control conditions. It is concluded that the mode of action of ADH is more complex than has been recognized hitherto and includes effects at the basolateral border.

Animals↗