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Biomedical subjects

S G Schultz

Publications and source records attributed to S G Schultz.

At least 55 records · Page 3Linked to original sources
PubMed1983

Relation between intracellular sodium and active sodium transport in rabbit colon: current-voltage relations of the apical sodium entry mechanism in the presence of varying luminal sodium concentrations.

The current-voltage relations of the amiloride-sensitive Na entry pathway across the apical membrane of rabbit descending colon, exposed to a high K serosal solution, were determined in the presence of varying mucosal Na activities, (Na)m, ranging from 6.2 to 99.4 mM. These relations could be closely fit to the "constant field" flux equation yielding estimates of the permeability of the apical membrane to Na, PmNa, and the intracellular Na activity, (Na)c. The following empirical relations emerged: (Na)c increased hyperbolically with increasing (Na)m; PmNa decreased hyperbolically with increasing (Na)m and linearly with increasing (Na)c; spontaneous variations in Na entry rate at constant (Na)m could be attributed entirely to parallel, spontaneous variations in PmNa; the rate of Na entry increased hyperbolically with increasing (Na)m obeying simple Michaelis-Menten kinetics; the relation between (Na)c and "pump rate," however, was sharply sigmoidal and could be fit by the Hill equation assuming strong cooperative interactions between Na and multiple sites on the pump; the Hill coefficient was 2-3 and the value of (Na)c at which the pump-rate is half-maximal was 24 mM. The results provide an internally consistent set of relations among Na entry across the apical membrane, the intracellular Na activity and basolateral pump rate that is also consistent with data previously reported for this and other Na-absorbing epithelia.

Animals↗
PubMed1983

Effects of Na-coupled alanine transport on intracellular K activities and the K conductance of the basolateral membranes of Necturus small intestine.

Intracellular electrical potentials and K activity, (K)c, were determined simultaneously in Necturus small intestine before and after the addition of alanine to the mucosal solution. As noted previously (Gunter-Smith, Grasset & Schultz, 1982), the addition of alanine to the mucosal solution resulted in a prompt depolarization of the electrical potential difference across the apical membrane (psi mc) and a decrease in the slope resistance of that barrier (rm). This initial response was followed by a slower repolarization of psi mc associated with a decrease in the slope resistance of the basolateral membrane (rs) so that when the steady state was achieved (rm/rs) did not differ significantly from control values in the absence of alanine. In the absence of alanine, psi mc averaged -32 mV and (K)c averaged 67 mM. When a steady state was achieved in the presence of alanine these values averaged -24 mV and 50 mM, respectively. The steady-state electrochemical potential differences for K across the basolateral membrane in the absence and presence of alanine did not differ significantly. Inasmuch as the rate of transcellular active Na transport or "pump activity" was increased two- to threefold in the presence of alanine, it follows that, if active Na extrusion across the basolateral membrane is coupled to active K uptake across that barrier with a fixed stoichiometry then, the decrease in rs must be due to an increase in the conductance of the basolateral membrane to K that parallels the increase in "pump activity". This "homocellular" regulatory mechanism serves to (i) prevent an increase in (K)c due to an increase in pump activity; and, (ii) repolarize psi mc and thus restore the electrical driving force for the rheogenic Na-coupled entry processes.

Alanine↗
PubMed1982

Stimulation of dome formation in MDCK kidney epithelial cultures by inducers of differentiation: dissociation from effects on transepithelial resistance and cyclic AMP levels.

Changes in transepithelial electrical resistance and cyclic nucleotide levels were monitored accompanying chemical induction of domes in a clonal subline of MDCK kidney epithelial cells. Confluent cell monolayers grown on nitrocellulose filters exhibited a relatively high mean transepithelial resistance (387 ohms X cm2). Hexamethylene bisacetamide, a potent inducer of dome formation (Lever, 1979b), stimulated significantly increased transmonolayer resistance as well as elevated levels of intracellular cyclic AMP. By contrast, dimethylformamide, an equally potent inducer of dome formation in MDCK cells, did not appreciably alter either resistance values or cyclic nucleotide levels. These results suggest that induction of dome formation in epithelial cell cultures by compounds generally known as inducers of differentiation may involve multiple and separate mechanisms.

Acetamides↗
PubMed1982

The electrophysiology of rabbit descending colon. II. Current-voltage relations of the apical membrane, the basolateral membrane, and the parallel pathways.

In this paper we employ the data described in the previous paper (I) to derive the current-voltage (I-V) relations of the basolateral membrane, the amiloride-insensitive "leak" pathway across the apical membrane, and the parallel pathways across rabbit descending colon. The results indicated that: a) The resistance of the basolateral membrane is independent of the electrical potential difference across that barrier over the range -8 to 67 mV and averaged 195 omega cm2. The electromotive force across this barrier averaged 50 mV under control conditions and 48 mV in the presence of amiloride. The origin of this difference is discussed. b) The resistance of the parallel pathways averaged 351 omegacm2 and was independent of the transepithelial electrical potential difference over the range -170 to + 90mV. The conductance of these pathways can be reasonably well accounted for by the partial ionic conductances of Na, K and Cl reported previously. c) The resistance of the amiloride-insensitive pathway across the apical membrane averaged 1667 omegacm2 and the electromotive force across this pathway averaged -51 mV. These values are in excellent agreement with those determined by others. The ionic nature of this "leak" pathway remains to be elucidated.

Amiloride↗
PubMed1982

Glucose absorption by in vitro perfused ileum of the fetal rat.

In vitro intraluminal perfusion of the fetal rat ileum at 19 and 20 days of gestation was employed to measure the rate of glucose absorption and the unidirectional fluxes of 3-O-methylglucose (3-O-MG). Fetal ileum was mounted on pipettes within an oxygenated bath and perfused with a solution containing glucose or 3-O-MG and polyethylene glycol with average molecular weight of 4,000 (PEG) as a marker substance. We verified that the PEG was not transported and did not diffuse across the fetal ileum. Scanning and electron microscopy before and after perfusion demonstrated preservation of mucosal anatomy. The rate of glucose absorption was 200 +/- 17 mumol.h-1.g-1 at 19 days and increased significantly to 378 +/- 12 mumol.h-1.g-1 at 20 days. The absence of sodium abolished this process. The flux of 3-O-MG from lumen to bath was 88 +/- 10 mumol.h-1.g-1 at 19 days and 160 +/- 16 mumol.h-1.g-1 at 20 days. Bath-to-lumen flux was -17 +/- 2 mumol.h-1.g-1 and did not vary with age. Active, rapidly developing transport of glucose and 3-O-MG is demonstrated by in vitro luminal perfusion of the fetal rat ileum at 19 days.

3-O-Methylglucose↗
PubMed1982

Nephrotoxicity of radiocontrast media in ischemic renal failure in rabbits.

Ischemic renal failure was produced in rabbits by occluding the renal arteries for 90 min. Group 1 (n = 8) received radiocontrast media at the time of occlusion, group 2 (n = 8) 24 h after occlusion, and group 3 (n = 8) 3 days after occlusion. Group 4 (n = 12) was subjected to ischemic injury alone, group 5 (n = 4) served as sham-operated controls and group 6 (n = 4) did not undergo surgery but received radiocontrast media. Serum creatinine concentration in group 1 increased to a greater degree (p less than 0.001) than all other groups and did not return to normal during the 8-day observation period. Creatinine concentration in groups 2, 3, 4, and 6 were comparable and significantly increased compared to sham-operated group (p less than 0.05). Urinary excretion of alanine aminopeptidase and N-acetyl-beta-glucosaminidase in group 1 was significantly greater than all other groups (p less than 0.05). Microscopic analysis indicated tubular necrosis was more prominent in group 1. Radiocontrast media is nephrotoxic and in the setting of ischemic injury may prevent recovery of renal function. Toxicity was dependent on the time of administration since functional impairment was not increased if dye was given 1 or 3 days after ischemic injury.

Acetylglucosaminidase↗
PubMed1981

Potassium transport across rabbit descending colon in vitro: evidence for single-file diffusion through a paracellular pathway.

The results of previous studies indicate that the bidirectional fluxes of K across short-circuited rabbit descending colon are attributable to passive diffusion through paracellular pathways and that this route is ten times more permeable to K than to Na and Cl. However, transepithelial diffusion potentials in the presence of large transepithelial Na and K concentration differences are much lower than those predicted by the "constant field equation" and appear to be inconsistent with this high K selectivity. The results of the present studies, designed to resolve this apparent contradiction, indicate that: (a) The ratios of the bidirectional transepithelial fluxes of K determined over a wide range of combined chemical and electrical potential differences conform reasonably well with those predicted by the Ussing flux-ratio equation. (b) The permeability coefficient of K (PK), determined from the net fluxes in the presence of concentration differences and from unidirectional fluxes under short-circuit conditions, decreases with increasing K concentration; in the presence of low K concentrations, PK is approximately ten-times PNa, but it approaches PNa in the presence of high K concentrations. PNa is not affected under these conditions. These results provide an explanation for the failure to observe large transepithelial diffusion potentials in the presence of large transepithelial Na and K concentration differences. In addition, these results are consistent with the notion that K diffuses across this preparation through two parallel pathways, one that does not discriminate among K, Na and Cl (a "free-solution" shunt) and another that is highly K selective and involves an interaction with one, or at most two, sites along the route.

Animals↗
PubMed1981

Some properties of KCl-filled microelectrodes: correlation of potassium "leakage" with tip resistance.

This study was undertaken in order to determine directly the rates of K leakage (JK) out of the tips of microelectrodes into a solution of 100 mM KCl (approximating the K concentration of the cell interior) and to relate these rates to the concentration of the filling solution and the tip resistance. The values of JK for electrodes filled with 3 M KCl having resistances of 16 and 30 M omega (when measured in 3 M KCl) were 10 and 5.5 fmol/sec, respectively. When the same electrodes were filled with 0.5 M KCl, the resistances (measured in 0.5 M KCl) increased to 62 and 115 M omega, respectively, and JK fell to 1.8 and 1.0 fmol/sec, respectively. These values are in reasonable agreement with what would be expected from theoretical considerations if leakage of KCl were the result of diffusion plus convective flow due to the hydrostatic pressure of the filling solution. We conclude that K leakage out of microelectrodes filled with 3 M KCl is unnecessarily high; leakage can be reduced fivefold by filling electrodes with 0.5 M KCl without incurring significant increases in tip or diffusion potentials or unmanageable tip resistances. Finally, the lowest rate of K leakage observed (1 fmol/sec) is still very considerable for the case of animal cells with an intracellular volume of approximately 1 pl and a K content of approximately 100 fmol. The finding of stable intracellular potentials, often for many minutes, in some tissues suggests that K which enters the cell rapidly diffuses into neighboring cells via high conductance intercellular communications.

Diffusion↗
PubMed1981

Homocellular regulatory mechanisms in sodium-transporting epithelia: avoidance of extinction by "flush-through".

In recent years electrophysiologic studies on several sodium-transporting epithelia have uncovered two "homocellular" (intrinsic) regulatory mechanisms that appear to protect the absorptive cells from marked changes in sodium and potassium content in response to rapid and wide-ranging physiologic variations in the rate of transcellular sodium transport. These are: 1) an inverse relation between intracellular sodium activity and the sodium conductance of the apical (mucosal) membrane, and 2) a parallel relation between the rate of sodium extrusion from the cell across the basolateral membrane ("pump activity") and the conductance of that barrier to potassium. The purpose of this review is to document these homocellular regulatory mechanisms, discuss their physiologic significance, and speculate on possible underlying mechanism(s).

Amiloride↗
PubMed1981

Potassium transport by rabbit descending colon, in vitro.

Studies of the bidirectional fluxes of K across segments of rabbit descending colon indicate that: a) when the tissue is short-circuited, the net flux does not differ significantly from zero under control conditions and in the presence of aldosterone; and b) the bidirectional fluxes of K conform to the Ussing flux-ratio equation over a wide range of transepithelial electrochemical potential differences. These and other findings strongly suggest that the movements of K across the epithelium are restricted to paracellular routes and are entirely passive. Studies dealing with the mechanism of homocellular K transport indicate that: a) K is actively transported into the cells across the basolateral membranes against an electrochemical potential difference of approximately 30 mV; and b) the active uptake of K may be mediated by a rheogenic Na-K exchange pump that is also responsible for transcellular Na transport. These results are entirely consistent with the model proposed by Koefoed-Johnson and Ussing for isolated frog skin.

Aldosterone↗
PubMed1981

Equivalent electrical circuit models and the study of Na transport across epithelia: nonsteady-state current-voltage relations.

After successfully impaling an absorptive cell of rabbit colonic epithelium with a microelectrode, "instantaneous" transepithelial current-voltage relations were determined under control conditions and in the presence of a maximally effective dose of amiloride. The results are interpreted using a very general equivalent electrical circuit model that admits the presence of an apical membrane conductance(s) to an ion(s) other than Na as well as the possibility of an incomplete action of amiloride on the Na entry step. The derived relation between the instantaneous Na current across that barrier conforms closely to the predictions of a simple, charged carrier model. The "reversal potential" of 64 mV is consistent with an intracellular Na activity of 11 nM. Finally, some of the implications of these findings are discussed with respect to 1) the applicability of linear models of active transepithelial Na transport, and 2) the experimental determinations and meanings of the "overall electromotive force" (ENa) and the "overall resistance" (RNa) of active Na transport.

Amiloride↗