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C J Edmonds

Publications and source records attributed to C J Edmonds.

106 records · Page 6Linked to original sources

Kinetics of potassium in colonic mucosa of normal and sodium-depleted rats.

1. The transport of K across the mucosal epithelium of the colon of normal and Na-depleted rats has been investigated in vivo by methods involving I.V. administration of solutions containing (42)K and by labelling the mucosa with (42)K from the lumen and observing the ;soaking-out' rates into radionucleide-free solutions.2. During the infusions, the specific activity of the mucosal K was always less than the simultaneous specific activity of the secreted K. On stopping the infusion the specific activity of the mucosal K fell although the plasma specific activity remained at all times greater than that of the mucosa. The blood flow rate to the mucosa estimated from these results was 0.95 ml./min.g wet wt.3. Experiments with (42)K in the lumen showed that the steady-state specific activity of the mucosal K was considerably less than expected if the K had been in a single compartment. The (42)K efflux curves were also consistent in showing two components. The curves were analysed on the basis of a model having two compartments in the mucosa with half-times of 6 and 33 min.4. Na depletion produced two significant changes, (a) K secretion rate doubled, (b) the steady-state specific activity of the mucosal K after luminal exposure to (42)K was increased. The half-times of the compartments were unaffected.5. The results were discussed in terms of a working hypothesis which represented the mucosal K in two compartments. Most of the K exchanges across the mucosa took place through the smaller compartment which probably contained 5% or less of the mucosal K, but which had a rapid turnover rate. The change of K permeability of the luminal face produced by Na depletion and probably due to increased aldosterone action, may well be an important factor in producing the rise of K secretion rate.

Animals↗

Use of a miniature GM counter and a whole body counter in the study of potassium transport by the colon of normal, sodium-depleted and adrenalectomized rats in vivo.

1. A method is described employing a whole-body counter and a miniature GM counter placed within the lumen of the gut which can be used to study the absorption rates and kinetics of labelled substances in the mucosal epithelium in vivo. The method was applied to the study of K transport by the mucosa of the descending colon of normal, Na-depleted and adrenalectomized rats.2. The K influx rate was linearly related to luminal [K] over the range 5-80 mM. NaCN in the lumen produced a fall of electrical potential difference (p.d.) and of K secretion rate but did not reduce K influx rate. The findings were consistent with passive K influx.3. The mucosal (42)K content reached a steady value after 60-90 min of exposure to (42)K in the lumen. The value was similar in normal and adrenalectomized rats but was greater in Na-depleted rats.4. After replacement of luminal solution by a non-radioactive solution the fall of mucosal (42)K content could be described, in the majority, by a curve having two exponential components with half-times of 8-10 and 65-106 min. Approximately half of the (42)K outflow passed to the lumen. The rate constants were similar in all groups of rats.5. The results analysed on the basis of representing the mucosal K as in two compartments, indicated that the observed absorption rate could not be accounted for by transport through these compartments alone and that most of the (42)K crossed the mucosa by a fast pathway not detectable by the miniature GM counter. Most of the mucosal K was relatively inaccessible from the lumen.6. Na depletion raised the transmucosal p.d., increased the K secretion rate and appeared to increase K permeability of the mucosa but the kinetics were unaltered. Accumulation of (42)K in the mucosa was greater, suggesting that the permeability of the luminal face had increased. Adrenalectomy produced only one change, namely a reduction of K secretion rate.

Adrenalectomy↗

Factors influencing the electrical potential across the mucosa of rat colon.

1. An investigation has been carried out into various factors which influence the transmucosal potential difference (p.d.) of rat colon in vivo when the p.d. is either high (> 30 mV) or low (< 20 mV).2. The p.d. was uninfluenced by short duration anaesthesia with ether or pentobarbitone. When anaesthesia was prolonged for several hours, p.d. rose steadily. The gradient of p.d. along the descending colon which developed and its elimination by adrenalectomy suggested that the rise was due to increased secretion of adrenal steroids.3. P.d. was increased by Na depletion after a delay of about 18 hr and fell again following Na repletion with a similar time delay. A characteristic gradient of p.d. along the descending colon was seen.4. Both haemorrhage and anoxia caused a rapid fall of p.d. P.d. was restored rapidly to its previous level when anoxia was corrected.5. Vasopressin (I.V.) in low dose was without effect; in high dose it caused a transient fall of p.d. associated with intense vasoconstriction of gut blood vessels.6. The following factors studied were without effect on p.d.: presence of glucose within the lumen; considerable osmotic gradients across the mucosa; variation of luminal pH over the range 5.2-9.8; intravenous administration of acetazolamide, chlorothiazide, frusemide, triamterene, ethacrynic acid or ouabain. Ouabain in the luminal solution also had no effect in all but two rats in which a small fall of p.d. was seen.7. 2,4-dinitrophenol, 10(-2)M, in the lumen caused a small fall of p.d. only if the p.d. was high.8. Experiments were done to determine the effect on p.d. of altering the ionic composition of the luminal solution. When the p.d. was low (< 20 mV) alteration of [Na], [K] or [Cl] produced small absolute changes of the p.d., all of comparable magnitude. The changes could be interpreted as due to diffusion potentials resulting from the ionic gradients across the mucosa. When the p.d. was high (> 30 mV), it showed a striking dependence on the luminal [Na] only, consistent with the presence of a large p.d. due to active Na transport.

Acetazolamide↗

Electrical potential and short circuit current of an in vitro preparation of rat colon mucosa.

1. Using a preparation of rat colon mucosa mounted in vitro in small chambers, some factors which influence the electrical properties of the mucosa have been investigated.2. The mucosa behaved mainly as an ohmic resistance although a very brief transient occurred on first passing current. At 32 degrees C, the fresh preparation had a mean resistance of 108Omega/cm(2) and a mean short circuit current (s.c.c.) of 143 muA/cm(2). Tissues taken from Na-depleted and adrenalectomized rats differed little from normal tissues in electrical resistance but those from Na-depleted rats had higher potential difference (p.d.) and s.c.c.3. Increase of temperature led to a rise of conductance of similar order to that found for ions in aqueous solution. S.c.c. also rose with increase of temperature but the effect was relatively greater consistent with its being dependent on metabolic processes.4. Anoxia or the addition of cyanide, iodoacetate or 2,4-dinitrophenol to the bath fluid caused considerable fall in the p.d. and s.c.c.5. Ouabain decreased the p.d. and s.c.c. when added to the serosal side but had no effect when on the luminal side.6. Aldosterone and acetazolamide had no effect.7. Varying serosal side [K] produced only minor changes in p.d.8. Reducing [Na] of the luminal solution caused a considerable fall of p.d. but similar reduction of [Na] on the serosal side had little effect.9. The frequently employed model which represents the transepithelial p.d. as the sum of diffusion potentials originating at the luminal and serosal sides of the cell layer is not consistent with the present results. The colonic transmucosal p.d. probably originates in the electrogenic transport of Na by a mechanism located on the serosal side of the epithelium.

Acetazolamide↗

The gradient of electrical potential difference and of sodium and potassium of the gut contents along the caecum and colon of normal and sodium-depleted rats.

1. The Na, K and water content of stools, and of gut contents removed from the terminal ileum, caecum and colon were determined in normal and Na-depleted rats and the p.d. across the colon wall measured at the site of removal of each specimen.2. During passage through the caecum and colon, especially the ascending segment of colon, the faecal Na and water content fell considerably, K content being unchanged in the normal rats and falling in the Na-depleted. Na concentration of the faecal water fell but K concentration rose owing to water absorption.3. Feeding normal rats with a sulphonated polystyrene resin caused a considerable Na loss in the stool, the ratio Na/(Na+K) being consistently greater than in rats not taking resin. Resin induced little Na but much K loss in Na-depleted rats.4. The electrical p.d. across the colon wall varied little over the length of the caecum and colon in normal rats, rarely exceeding 20 mV, the serosa being +ve with respect to lumen. Potential difference measurements were greater in Na-depleted rats, and those of the caecum and descending colon were consistently higher than those of the ascending colon. There was a similar pattern in resin-fed rats but potentials tended to be higher.5. K concentration of the gut contents was always greater than could be accounted for if K were passively distributed across the colonic mucosa.6. It was concluded that: (i) active Na absorption was stimulated by Na depletion; (ii) K was probably actively transported into the colon lumen, and when unabsorbable anions were present in the gut K secretion was critically important in Na absorption; (iii) the elevation of p.d. associated with Na depletion was probably associated with the stimulated Na transport.

Journal Article↗

Transport of sodium and secretion of potassium and bicarbonate by the colon of normal and sodium-depleted rats.

1. Ascending and descending colonic segments of normal and Na-depleted rats were perfused in vivo with isotonic solutions of varying Na concentration and the unidirectional Na fluxes and secretion rate of K and bicarbonate and the transmucosal electrical p.d. were measured.2. Potential difference was greater in Na-depleted rats, especially towards the distal end of the descending colon. With reduction of luminal Na concentration, p.d. was reduced.3. The ascending and descending segments were similar in regard to Na transport except that the latter had lower passive permeability. Na depletion caused an increase of Na influx rate, Na net flux rate and Na exchange diffusion whilst the mucosal passive Na permeability decreased. These changes resulted in a reduction in the critical luminal Na concentration, i.e. the concentration at which the unidirectional fluxes were equal.4. K secretion rate was similar in the ascending and descending colon and was increased by Na depletion. In all rats, it was reduced when the luminal Na concentration was low.5. Bicarbonate secretion rate was unaffected by the Na depletion and all solutions remained isotonic during perfusion.6. The results confirmed that active Na transport was stimulated by Na depletion but indicated that this was probably not the only factor in the elevation of transmucosal p.d.

Journal Article↗

Transport of potassium by the colon of normal and sodium-depleted rats.

1. Ascending and descending segments of colon of normal and Nadepleted rats were perfused with solutions of differing KCl concentration. Net K flux, electrical p.d. and, in some experiments, unidirectional K fluxes were measured.2. Variation of luminal K concentration over the range 0-40 mM did not affect p.d. or K efflux rate.3. K secretion rate fell about 30% when Na-free choline chloride solution was perfused.4. Net flux was a linear function of the luminal K concentration, and fell as the latter increased. Na depletion increased K secretion rate and passive permeability of the mucosa to K. Adrenalectomy had the reverse effect. The luminal K concentration, associated with zero net K flux was much greater than expected if the colonic mucosa behaved passively with respect to K.5. Unidirectional fluxes determined when 5 mM-KCl was in the lumen showed that the ratio influx/efflux was much less than predicted by Ussing's flux ratio equation.6. It was concluded that K influx was due to simple diffusion and K efflux to diffusion and active transport, both processes being increased by Na depletion.

Journal Article↗