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E Frömter

Publications and source records attributed to E Frömter.

At least 109 records · Page 6Linked to original sources
PubMed1983

Functional properties of the paracellular pathway in some leaky epithelia.

We here review the functional properties of the paracellular pathway of leaky epithelia such as gallbladder and renal proximal tubule. These epithelia are characterized by leaky terminal bars between adjacent cells which allow small ions, non-electrolytes and water to leak from lumen to interstitial fluid or back. In the past 10 years a great deal of information has been obtained about the properties of the misnamed 'tight' junctions in the terminal bars, by assuming that the overall permeation pattern reflected predominantly the junctional permeation properties. Although recent trans- and intraepithelial impedance analyses indicate that this assumption is not always justified (the contribution of the lateral intercellular space to the paracellular shunt resistance is not negligible, when the spaces are collapsed) it seems that the major conclusions are correct. The properties of the terminal junctions may thus be summarized as follows. (1) Large molecules such as horseradish peroxidase are not able to pass. (2) Passage of lipophilic substances is insignificant, as these substances permeate by the cellular route. (3) Depending on the tissue, ion permeation is either governed by channels with negative fixed charges, or positive fixed charges, or both. As inferred from ion selectivity patterns the channels of different epithelia are either wide and highly hydrated or narrow and poorly hydrated, thus allowing more or less water molecules to pass besides the ions. In narrow channels single-file diffusion may occur. (4) Besides the selective channels a free solution shunt seems to be present in some epithelia. (5) When applied in millimolar concentrations 2,4,6-triaminopyrimidinium and amiloride block negatively charged junctional channels. However these substances do not simply turn leaky epithelia into tight epithelia, because they have additional effects on the cell membranes. (6) As observed in cell cultures, formation of tight junctions requires connecting particles to be present on the cell surface--which seems to be controlled by the cytoskeleton-- and requires the presence of calcium ions as ligands. (7) Cellular control over paracellular permeability may be exerted through changes of intracellular calcium concentration.

Animals↗
PubMed1983

pH--dependence of phosphate absorption in rat renal proximal tubule.

Proximal tubular cell membrane potentials were measured in rat kidney in vivo and the response to luminal perfusion of 2mmolar phosphate (Pi) was studied. Pi transport was preferentially rheogenic at low pH (cotransport of 1H2PO2- plus 2Na+) but preferentially electroneutral at high pH (cotransport of 1HPO4--plus 2Na+). The potential response as a function of pH conformed to a model which transports both H2PO4- and HPO4--indiscriminately and whose maximal transport capacity increases with increasing pH. Further kinetic experiments are required to definitely exclude separate transport systems for both ionised forms. Hypercapnic phosphaturia may be explained by a decreased maximal transport capacity of Pi at low luminal pH.

Animals↗
PubMed1982

A simple method for constructing shielded, low-capacitance glass microelectrodes.

A new simple method is presented to produce shielded low-capacitance microelectrodes. A metal-shield is vapour-deposited on the inner surface of a glass pipette which is slid over the microelectrode proper and insulated at the tip by dipping in polystyrene. The unshielded protruding tip can be as small as 10 micrometers. A special advantage is the low capacitance between electrode and shield of approximately 0.16 microF/cm shield length.

Glass↗
PubMed1982

Square wave pulse analysis of cellular and paracellular conductance pathways in Necturus gallbladder epithelium.

In search for a rapid and reliable method to identify and quantitatively determine cell membrane resistances and paracellular shunt resistances in epithelia we have developed appropriate techniques to measure transepithelial and intracellular potential transients in response to transepithelially applied square wave constant current pulses. Model considerations indicate that in a unilayered, homogeneous epithelium with open lateral spaces the transient potential response across each cell membrane should obey a single exponential function in case the tight junction resistance is high, as in a tight epithelium, whereas in a leaky epithelium it should consist of a superposition of two exponentials with equal sign at the membrane with the higher intrinsic time constant and of two exponentials of different sign (overshoot with recline) at the membrane with the lower intrinsic time constant. The latter predictions were experimentally verified in a study on Necturus gallbladder epithelium and equivalent circuit parameters for the cell membrane resistances and capacitances as well as for the resistance of the shunt path were calculated from the data by curve fitting procedures. The resistances of the apical and basal cell membrane and of the shunt path averaged 1220, 201 and 91 omega cm2 respectively while the apical and basal cell membrane capacitances were 8.0 and 26.3 micro F/cm2 respectively. The fact that the resistance values are 4-15 times lower than estimates derived previously from 2D-cable analysis relates to a better preservation of the transport function under the present incubation conditions as verified by a new series of cable analysis data. The capacitances agree well with estimates of the surface amplification of the cell membranes from electronmicrographs, thus confirming the validity of the interpretation of the observed voltage transients.

Animals↗
PubMed1982

Electrophysiological analysis of rat renal sugar and amino acid transport. I. Basic phenomena.

The electrical events associated with the absorption of D-glucose or L-amino acids in renal proximal tubules were studied in microperfusion experiments on rat kidneys in vivo. Intratubular application of these substrates led concomitantly to: 1) a shift of the transepithelial potential into lumen negative direction, 2) a partial depolarization of the tubular cell membranes and 3) a reduction of the electrical resistance of the brushborder membrane. By means of rapid perfusion experiments it was possible to discern two phases in the potential response to substrate perfusion, a fast initial response which reflects a substrate-induced Na+ ion current from lumen to cell, and a slower secondary response which reflects the relaxation of the intracellular ion and substrate concentrations towards new steady states. A quantitative analysis of the data yielded estimates of 1) the apical (Ra) and basal (Rb) cell membrane resistances and of the shunt resistance, Rs, of rat proximal tubule of approximately Ra = 255 omega cm2, Rb = 92 omega cm2 and Rs = 5 omega cm2 (all referred to the quasi macroscopic surface area of the tubular lumen), 2) the conductance of the Na+ and glucose cotransport pathway and 3) the driving forces acting on the cotransport mechanism in the brushborder membrane. The latter were found to be a) the electrical cell membrane potential of -74 mV, b) the Na+ ion concentration gradient between the tubular lumen (clumNa = 145 mmol/l) and the cytoplasm (ccellNa approximately 33 mmol/l) which corresponds to an additional equivalent potential of 51 mV and c) the substrate concentration gradient, which varies according to the experimental conditions. Moreover the analysis provided a quantitative estimate of the relationship between the substrate-induced changes in transepithelial potential or short circuit current and the actual cotransport current in the brushborder membrane. Based on this analysis it is concluded that the stoichiometry of Na+ and glucose flux coupling in the brushborder membrane of rat proximal tubule is close to 1.0.

Amino Acids↗
PubMed1982

Electrophysiological analysis of rat renal sugar and amino acid transport. II. Dependence on various transport parameters and inhibitors.

Transepithelial and cellular electrical potential changes were measured in response to luminal perfusion of D-glucose and related substrates in micropuncture experiments on rat kidney in vivo. By studying the dependence of the potential response on various experimental parameters, some insight was obtained into the mechanism of Na+ coupled glucose absorption. The experiments confirm the driving forces for glucose absorption in the living cell to be: a) the Na concentration gradient, b) the electrical potential gradient and c) the glucose concentration gradient across the brush-border membrane. Furthermore they describe the substrate specificity of the cotransport mechanism and the mechanism of inhibition of D-glucose transport by various inhibitors, such as phlorizin, harmaline and ouabain. The latter experiments suggest that the active Na+ pump in the peritubular cell membrane, which establishes the Na+ ion gradient and the electrical potential gradient across the brushborder, contributes a measurable partial conductance to the overall electrical conductance of the peritubular cell membrane.

Acetazolamide↗
PubMed1982

Electrophysiological analysis of rat renal sugar and amino acid transport. IV. Basic amino acids.

Electrophysiological techniques were used to study the transport of the basic amino acids L-arginine, L-lysine and L-ornithine in rat kidney proximal tubule in vivo. Tubular cells were punctured with microelectrodes and the response of the cell membrane potential to sudden applications of the amino acids was measured. In the presence of physiological Na+ concentrations luminal perfusion with millimolar concentrations of basic amino acids depolarized the tubular cells in a concentration dependent fashion by up to 15 mV, while in the absence of Na+ no significant potential changes were observed. These observations indicate that the basic amino acids are taken up into the cell across the brushborder in coupling with Na+ ions in a similar way as neutral and acidic amino acids, and that simple conductive pathways for uncoupled flow of the basic amino acids do either not exist or are quantitatively negligible in the brushborder. From kinetic measurements and competition experiments it was concluded that all basic amino acids are transported by the same transport system, which however does not accept acidic or neutral amino acids (with the possible exception of L-cystine). Perfusion of the peritubular capillaries with millimolar concentrations of basic amino acids depolarized the cells only by approximately 1 mV, both in the presence and absence of Na+. This observation may indicate that a passive uncoupled transport pathway for basic amino acids is present in the peritubular cell membrane to allow exit from cell to interstitial space, if the intracellular concentration rises high enough to overcome the cell membrane potential.

Amino Acids↗
PubMed1982

Electrophysiological analysis of rat renal sugar and amino acid transport. V. Acidic amino acids.

We have used electrophysiological techniques to study various aspects of the transport of glutamate and aspartate in proximal tubules of the rat kidney in vivo. Single tubular cells were punctured with microelectrodes and the response of the cell membrane potential to sudden luminal or peritubular applications of these amino acids was measured. The experiments indicated that a specific transport system exists for L-glutamate and L-aspartate in the brushborder membrane, which does not transport neutral or basic amino acids. The uptake of both L-amino acids from the lumen into the cell was found to be rheogenic, probably reflecting the cotransport of two Na+ ions together with one amino acid molecule. The transport system has a slightly greater affinity for L-glutamate, but transports the smaller L-aspartate somewhat faster. Besides the L-isomers also D-glutamate and D-aspartate were found to depolarize the tubular cells which suggests that also the D-isomers are absorbed in the tubule, however they do not seem to use the same transport system as the L-isomers. In addition to the transport system in the brushborder, a similar Na+-dependent, rheogenic transport system for L-glutamate and L-aspartate was also found in the peritubular cell membrane, as deduced from cell cell depolarizations in response to these substrates applied peritubularly. The simultaneous presence of Na-driven transport systems in the apical and basal cell membrane which is not found with other amino acids, may explain the high intracellular accumulation of L-glutamate and L-aspartate in the kidney and provides a rational basis for explaining clinically observed cases of dicarboxylic aminoacidurias.

Amino Acids↗
PubMed1979

[Principles of epithelial transport in the kidney and intestines].

Epithelia of kidney and small intestine consist of one layer of cells which, at their luminal edge, are linked together by terminal bars. Solute transport proceeds either across the cells, which is true of all active transports, or it proceeds paracellularly through the basolateral spaces and terminal bars and is then passive. The driving force for the active transport of a substance is derived either directly from metabolism (primary active transport), or from the gradient of another solute, usually Na+, which in turn is created by primary active transport. In the latter case the transport is referred to as secondary active. The driving forces of passive transport are the electrochemical gradient of the respective substance and solvent drag. The proximal parts of the kidney as well as of the intestine are leaky so that a considerable part of net reabsorption proceeds passively. Their distal parts, however, where the transport is regulated, are tight so that large concentration differences can be created and maintained. Transcellular active transport is only possible if the cells are polar, i.e., the transport characteristics of the luminal cell membrane differ from those of the contraluminal cell membrane. By measuring the cellular electrical potential difference or by measuring transport into isolated plasma membrane vesicles from either cell side the driving forces for the two transport steps, the luminal and contraluminal, have been elucidated. Schemes for the transport steps in the proximal tubule and in the small intestine are given. They show the principal similarity of the transport of many substances in both epithelia.

Absorption↗
PubMed1978

The AC impedance of Necturus gallbladder epithelium.

The impedance of Necturus gallbladder epithelium was determined using sine wave currents of 1 Hz to 30 kHz. In control Ringer's solution the impedance locus exhibited a simple semicircle with minute shift of the high frequency end along the real axis and a minute depression of the center below the real axis (average 0.9 +/- 0.7 degrees). Neglecting the slight suppression, the impedance of 1 cm2 of epithelium can be represented by an electrical analogue consisting of a parallel RC element of 115 +/- 26 omega and 5.16 +/- 0.9 muF in series with a small resistor of 5.3 +/- 1.3 omega. In agreement with experimental results obtained under ionic or osmotic substitutions, the applicability of this simple RC analogue to gallbladder epithelium under control conditions can be explained by the influence of the paracellular shunt and by assuming the time constants of the apical and basal cell membranes to be comparable. Based on these data and on voltage divider measurements obtained with microelectrodes the capacitances of the apical and basal cell membrane can be estimated to be approximately 7 and approximately 18 muF/cm2. The latter value agrees well with estimates of the surface folding obtained from electromicrographs, if the specific cell membrane capacitance is assumed to be approximately 1 muF/cm2 as in other cell membranes.

Animals↗