Abstract:SUMMARY1. The kinetics of 24Na exchange in rat cerebrospinal fluid, brain and sciatic nerve were studied during steady-state plasma isotope conditions. The entrance of 24Na into brain and sciatic nerve was found to fit a three compartmental model. Using newly derived equations for compartmental analysis, the first compartment 24Na space of brain was found to be about 22 % and the second compartment space about 6 %; the corresponding sciatic nerve spaces were 26 and 11 %, respectively. In the discussion, argume… Show more
“…This results in a significant advantage for data analysis in comparison to compartmental analysis, since the results for any compartmental analysis are highly specific for the particular compartmental model chosen. An illustration of this problem is provided by Levin and Patlak (1972). These authors used two different compartmental models and pro duced two different sets of transfer numbers from their data.…”
Summary: A theoretical model of blood -brain exchange is developed and a procedure is derived that can be used for graphing multiple-time tissue uptake data and deter mining whether a unidirectional transfer process was
“…This results in a significant advantage for data analysis in comparison to compartmental analysis, since the results for any compartmental analysis are highly specific for the particular compartmental model chosen. An illustration of this problem is provided by Levin and Patlak (1972). These authors used two different compartmental models and pro duced two different sets of transfer numbers from their data.…”
Summary: A theoretical model of blood -brain exchange is developed and a procedure is derived that can be used for graphing multiple-time tissue uptake data and deter mining whether a unidirectional transfer process was
“…However, the results from any compartmental analysis of experimental data are highly specific for the particular com partmental model chosen. Levin and Patlak (1972) demonstrated this limitation by obtaining two dif ferent sets of transfer numbers from an analysis of their data by two different compartmental models.…”
We have argued that the most accurate and reli able way of measuring unidirectional blood-to-brain transfer constants employs graphical analysis of the tissue-uptake data obtained from a number of mea surements or experiments of differing duration (multiple-time/graphical analysis) (Fenstermacher et aI., 198 1; Blasberg et aI., 1983; Patlak et aI., 1983). The advantages of the multiple-time/ graphical approach include the ready assessment of the unidirectional uptake phase, the ease and ac curacy with which the tissue data are corrected for the amount of the test substance that has not com pletely crossed the blood-brain barrier (BBB), and the production of a relatively model-independent transfer constant.
“…To further examine the effect of FBS removal, we calculated the parameters of a serial, three-compartmental model (Levin and Patlak, 1972). The pool sizes of a three-compartmental model in parallel were also calculated as given by Smith et al (1979).…”
Section: Effect Of Fbs Removal On 22naf Washoutmentioning
In order to elucidate changes in cell transport behavior of cultured human skin fibroblasts in response to acute serum depletion, we performed uptake and washout of 22Na+ and 86Rb+ as well as measurements of the intracellular Na+ and K+ levels in the presence and absence of ouabain. Pronounced and lasting increase in cellular Na+ and decrease in K+ were observed after removal of fetal bovine serum (FBS) from the medium. The sum of the Na+ and K+ contents (nEq/10(5) cells) was lower in FBS-free medium (mean +/- SD; 17.3 +/- 2.2) than in FBS-containing medium (26.2 +/- 3.8; P less than .02). Simultaneously, a decrease in cellular water volume was detected in the FBS-free medium. The cation uptake and washout data suggest that FBS removal primarily renders the cells more permeable to Na+ and K+ with a secondary stimulation of the ouabain-sensitive Na+ extrusion mechanism. FBS at a concentration of 0.2% prevented approximately 50% of the maximal increase in the 86Rb+ washout rate constant associated with FBS depletion. Ouabain (2 microM) produced an increase in the 86Rb+ washout rate constant. This effect was substantially larger in cells subjected to medium without FBS (from 0.0303 to 0.2500 min-1) than in fibroblasts incubated in medium with FBS (from 0.0107 to 0.0487 min-1). The cellular K+ content was drastically reduced by ouabain to a level not different in medium with or without FBS (33.9 +/- 4.5 to 1.75 +/- 0.38 and 16.7 +/- 1.4 to 1.4 +/- 0.13 nEq/10(5) cells, respectively). The 22Na+ washout data exhibited a three-exponential pattern. Analytical solutions of the washout data by means of two models (serial and parallel) with three compartments showed that FBS depletion resulted in increase of the size of all three compartments. It is concluded that in cultured human skin fibroblasts, FBS is essential to the maintenance of a normal Na+ and K+ homeostasis. The removal of FBS results in dramatic permutation of this homeostasis that develops within minutes and lasts for hours.
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