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The "glial impairment hypothesis" states that astrocytes which change from normal into the reactive type lose their ability to clear extracellular K+, which in turn leads to hyperexcitability in the gliotic tissue. As this hypothesis was never proven or disproven, the question of glial efficiency in K+ clearance in gliotic tissue is still controversial, mainly due to the lack of direct measurements of the intracellular K+ concentration of reactive astrocytes. In order to investigate K+ accumulation by glial cells of gliotic tissue, we used hippocampal slices. Adult rats, previously treated with kainic acid, exhibited loss of neurons and gliosis in the CA1 layer of the hippocampus within 3 days. After this time period, double-barrelled microelectrodes were used to inject Lucifer yellow into cells of the stratum radiatum of the CA1 subfield in 400-microm-thick hippocampal slices. These cells had electrophysiological and morphological characteristics of astrocytes. Most injected cells (70%) were dye-coupled to other cells and were glial fibrillary acidic protein (GFAP)-positive (80%). We found, however, that GFAP-positive cells were dye-coupled not only to each other, but also to GFAP-negative cells. In another set of experiments, we investigated the glial membrane potential during reduction of the extracellular Cl-concentration and the use of the Cl- channel blocker 4,4'-diisothiocyanostilbene-2,2' disulphonic acid (DIDS). The results suggest that reactive astrocytes have a significant resting Cl- conductance. K+-selective microelectrodes were used to analyze the intracellular glial K+ concentration. When the extracellular K+ concentration was increased from 3.5 mM to 10 mM, the intracellular K+ concentration increased by 23 mM. Experiments in which different ion transport systems were blocked with ouabain and DIDS suggest that this increase is dependent on two mechanisms, which can substitute each other: the Na+, K+-ATPase and passive K+ and anion fluxes. Inhibition of either of the two mechanisms did not block the K+ uptake. If, however, the Na+, K+-ATPase and Cl- channels were inhibited at the same time, the net accumulation of K+ was blocked. It appears, therefore, that astrocytes in the gliotic stratum radiatum of the hippocampal slice have the capacity to limit increases in extracellular K+ that are produced by hyperactive surviving hippocampal neurons by passive mechanisms and hence independently of blood and oxygen supply.

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The present investigation addresses the pharmacokinetics of human chorionic gonadotropin (hCG), intramuscularly (i.m.) administered to goats. Nine pluriparous does of the Boer goat breed, 2-6 years of age and weighing 45-60 kg, were administered 500 IU hCG (2 ml Chorulon) deep into the thigh musculature 18 h after superovulatory FSH treatment. Blood samples were drawn from the jugular vein at 2 h intervals for the first 24 h, at 6 h intervals until 42 h, and at 12 h intervals until 114 h after administration. After centrifugation, plasma hCG concentrations were determined by electrochemiluminescence immunoassay. Pharmacokinetical parameters were as follows: lag time, 0.4 (S.E.M. 0.1) h; absorption rate constant, 0.34 (S.E.M. 0.002) h; absorption half-life, 2.7 (S.E.M. 0.5) h; elimination rate constant, 0.02 (S.E.M. 0.002) h; biological half-life, 39.4 (S.E.M. 5.1) h; and apparent volume of distribution, 16.9 (S.E.M. 4.3) l. The plasma hCG profile was characterized by an absorption phase of 11.6 (S.E.M. 1.8) h and an elimination phase of 70.0 (S.E.M. 9.8) h, with considerable individual variation in bioavailability and pharmacokinetical parameters. Biological half-life was negatively correlated (P!0.05) with peak concentration (rZK0.76), absorption rate constant (rZK0.78), and elimination rate constant (rZK0.87). The results indicate that after rapid absorption, hCG remains in the circulation for an extended period. This has to be taken into account when assessing the stimulatory response to hCG treatment on an ovarian level.

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