Erythrocytes possess a Cl-dependent, Na-independent K transport system cotransporting K and Cl in a 1:1 stoichiometry that is membrane potential independent. This K-Cl cotransporter is stimulated by cell swelling, acidification, Mg depletion, and thiol modification. Cell shrinkage, elevation of cellular divalent ions, thiol alkylation, phosphatase inhibitors, and derivatives of certain loop diuretics and stilbenes are inhibitory. Thus regulation of K-Cl cotransport at the membrane and cytoplasmic levels is highly complex. Basal K-Cl cotransport decreases with cellular maturation, whereas its modes of stimulation and inhibition are variable between species. The physiological inactivation appears to be prevented in low-K animal erythrocytes. In certain human hemoglobinopathies, K-Cl cotransport may be the cause of cellular dehydration and volume decrease. K-Cl cotransport occurs also in nonerythroid cells, such as in epithelial and liver cells of other species. At the threshold of molecular characterization, this comprehensive review places our present understanding of the mechanisms modulating K-Cl cotransport physiologically and pathophysiologically into kinetic and thermodynamic perspectives.
The thickness of the unstirred water layer in in vivo-lavaged canine jejunum has been estimated by observations on the kinetics of entrance of [14C]inulin into the intervillus space (IVS) from the luminal fluid. Concentrations of the inulin in the IVS at three different levels (upper, 350 micrometers; middle, 250 micrometers; and lower, 250 micrometers) were determined as a function of duration of lavage. The concentrations rose slowly, indicating that there was little or no convective mixing of the fluid between the villi. After 1-2 h of lavage, mean concentrations in the IVS were three to seven times higher than in the lavage fluid, indicating that water absorption occurred from the IVS and that solvent drag as well as diffusion played a role in the entrance of inulin into the IVS. Because the concentration was always greatest at the uppermost level of the IVS, water absorption from the IVS must have been restricted to that level. Analysis of the data also required the inclusion of a small secretory stream (5% of the absorptive flow) from the crypts to explain the experimental observations. The results demonstrate that substances absorbed into the villus tips must penetrate an unstirred layer of 500-1,000 micrometers; for those absorbed into the lateral surfaces of the villi, an additional barrier of as much as 800 micrometers exists.
The kinetic parameters and transport mechanism of Na-Li exchange were studied in both low K (LK) and high K (HK) sheep red blood cells with cellular Na [( Na]i) and Li concentrations [( Li]i) adjusted by the nystatin technique (Nature New Biol. 244: 47-49, 1973 and J. Physiol. Lond. 283: 177-196, 1978). Maximum velocities (Vm) for Li fluxes and half-activation constants (K1/2) for Li and Na of the Na-Li exchanger were determined. The K1/2 values for both Li and Na appeared to be similar in both cell types, although they were about two to three times lower on the inside than on the outside of the membrane. Furthermore, the K1/2 values for Li were at least an order of magnitude smaller than those for Na, suggesting substantial affinity differences for these two cations. The Vm values for Li fluxes, on the other hand, appear to be lower in HK than in LK cells. When Na and Li fluxes were measured simultaneously, a trans stimulatory effect by Na on Li fluxes was observed. From measurements of Li influx at different concentrations of external Li and different [Na]i, the ratio of the apparent Vm to the apparent external Li affinity was calculated to be independent of [Na]i for both types of sheep red blood cells. Similar trans effects of external Na were observed on Li efflux at varying [Li]i. These results are expected for a system operating by a "ping-pong" mechanism.
The effects of hyperthermia on the content of lactic acid and beta-hydroxybutyric acid in the SCK mammary carcinoma and the leg muscle of A/J mice were studied. The contents of lactic acid in the SCK tumour before heating was 9.32 mumol/g, and the content of beta-hydroxybutyric acid was only 0.013 mumol/g. The lactic acid content in the tumour increased to 17.5 mumol/g at 0 h after heating at 41.5 degrees C for 30 min and then decreased to the control level 3 h later. When heated at 43.5 degrees C for 30 min, the lactic acid content in the tumour increased to 24 mumol/g at the end of heating and remained elevated for 24 h. The content of beta-hydroxybutyric acid increased continuously reaching 0.45 mumol/g at 5 h after heating at 43.5 degrees C for 30 min, and then declined thereafter. The contents of lactic acid and beta-hydroxybutyric acid in the muscle also increased after heating, but these increases were far less than those observed in the tumours. The absolute amount of lactic acid in the heated tumours was far greater than that of beta-hydroxybutyric acid, and thus appeared to play the major role for the increased acidity in the heated tumours.
The possibility of countercurrent exchange of water molecules in canine intestinal villi has been examined. Tritium-labeled water (3H2O) molecules were introduced either into the fluid lavaging the intestinal lumen or into the arterial blood supply for varying periods of time. Quickly frozen samples of intestinal tissue were sectioned such that isotopic concentrations at the villus tip, midvillus, villus base, and underlying submucosa and muscle could be determined. The villus concentration gradients observed were consistent with the existence of a countercurrent exchange but could also be explained by alternative arrangements. More convincing evidence of a countercurrent was obtained from experiments in which [14C]inulin was introduced simultaneously with 3H2O into the intestinal artery. The villus tip-to-base concentration ratio for 3H2O was less than one while the ratio for inulin was greater than one, thus vitiating the alternative explanations and leading to the conclusion that the labeled water molecules must have undergone a countercurrent exchange.
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