Biomedical subjects

D Hoppe

Publications and source records attributed to D Hoppe.

At least 37 records · Page 2Linked to original sources

PubMed1989

GABA triggers a Cl- efflux from cultured mouse oligodendrocytes.

gamma-Aminobutyric acid (GABA) has been shown to depolarize the membranes of astrocytes and oligodendrocytes taken from different tissues and species. The mechanism mediating this depolarization was identified, in cultured rat brain astrocytes, as an activation of GABA receptor-linked Cl- channels. A subpopulation of cultured oligodendrocytes from mouse spinal cord also responded to GABA with a membrane depolarization. In the present study we demonstrate that, in oligodendrocytes, the depolarization was accompanied by a decrease in intracellular Cl- activity [( Cl-]i) as measured with ion-selective microelectrodes. At rest, [Cl-]i was elevated above the passive distribution, and upon application of GABA, [Cl-]i decreased towards the level of passive distribution. Furosemide blocked the Cl- inward carrier which led to a passive Cl- distribution; in the presence of furosemide, GABA no longer elicited a membrane depolarization or a change in [Cl-]i. We conclude that oligodendrocytes, which were depolarized by GABA, expressed GABA-activated Cl- channels. Oligodendrocytes which were unresponsive to GABA demonstrated a non-passive Cl- distribution indicating that they did express inward-directed Cl- carriers, but no GABA-activated Cl- channels.

Animals↗

PubMed1989

Carrier-mediated Cl- transport in cultured mouse oligodendrocytes.

We studied the steady state and the regulation of intracellular Cl- activity (aCl-i) and the mechanisms of KCl uptake in cultured oligodendrocytes from mouse spinal cord using Cl(-)-selective microelectrodes. The majority of oligodendrocytes actively accumulated Cl- above passive distribution (2-3 mM), few cells showed a passive Cl- distribution. To identify the carriers mediating Cl- uptake, oligodendrocytes were maintained in a solution with low extracellular Cl- concentration ([Cl-]o) which resulted in a rapid decrease in aCl-i. The recovery of aCl-i above its passive distribution in normal [Cl-]o was blocked in the absence of Na+ or in the presence of furosemide and of bumetanide, which has been reported to inhibit Na+/K+/Cl- cotransport. We therefore conclude that Cl- uptake is primarily due to the activity of a Na+K+/Cl- transport system. Cl- uptake above passive distribution was not affected in HCO3(-)-free solution or in the presence of SITS and DIDS, indicating that Cl-/HCO3- exchange is not involved in Cl- uptake by oligodendrocytes. Elevation of [K+]o induced an increase in aCl-i and, as shown earlier, intracellular K+ activity. This K+-induced Cl- uptake was not blocked by bumetanide, furosemide, SITS, or DIDS, suggesting that under conditions of raised [K+]o the combined uptake of K+ and Cl- is not mediated by a carrier, but can be explained by the entry through channels driven by Donnan forces.

Animals↗

PubMed1989

Glial cells of the oligodendrocyte lineage express proton-activated Na+ channels.

Neurons and oligodendrocytes, but not type I astrocytes and Schwann cells, generate large Na+ currents in response to a step increase of [H+]. Proton-activated Na+ channels are the first cationic channels expressed in neuronal precursor cells from the mammalian brain. Glial precursor cells cultured from mouse brain are also capable of generating Na+ currents in response to step acidification (INa(H]. With further development along the oligodendrocyte lineage, this property is retained, whereas voltage-activated Na+ and K+ currents disappear. Comparing INa(H) of oligodendrocytes with INa(H) of their precursor cells did not reveal a difference in current amplitude, suggesting a higher density of INa(H) channels on the (smaller) precursor cells. The properties of INa(H) in glial precursor cells and oligodendrocytes are similar to those of neurons, with respect to activation conditions, time course, and the effect of extracellular Ca2+ concentrations. The results are consistent with previous observations which showed that oligodendrocytes partially preserve their chemically activated, but completely lose their voltage-activated, ion channels.

Animals↗

PubMed1989

Activation of K+ currents in cultured Schwann cells is controlled by extracellular pH.

We analyzed the pH dependence of K+ currents recorded with the patch-clamp technique from cultured Schwann cells obtained from mouse dorsal root ganglia. Currents were activated at potentials more positive than -50 mV which was close to the resting membrane potential. Current amplitudes were affected by a change in extracellular pH (pHo), being increased at alkaline, and decreased at acidic pHo. The strongest effect of a pHo change was observed on currents activated close to the resting membrane potential suggesting a functional role for the pH sensitivity of K+ currents. Analysis of the time course of current activation at different pHo values led to the conclusion that the pH-sensitivity of K+ currents in Schwann cells is due to changes in surface charges shifting the potential sensed by the gating process of the channel. The reversal potential of the currents was not affected by a change in pHo. This observation and the finding that even a strong acidification to a pHo value of 5.0 did not lead to a blockade of the fully activated channel, indicate that the pH-sensitive charges are not located in the channel pore. Under the assumption that pHo changes in a peripheral nerve are associated with nerve activity as in the optic nerve, the pH-sensitive K+ channel in Schwann cells could serve to facilitate the spatial buffering of extracellular K+.

4-Aminopyridine↗

PubMed1989

Salivary gland myoepithelioma variants. Histological, ultrastructural, and immunocytological features.

The histological and ultrastructural features of five major salivary gland tumours, which have little or no evidence of duct- or gland-type differentiation in routine sections, are described. Four of the cases have the tumour cells organized as narrow, anastomosing cords of cells separated by a myxoid and vascularized stroma; we have designated such lesions as reticular-type myoepitheliomas. The fifth case has a solid growth pattern and is largely composed of hyaline cells, that is, a plasmacytoid myoepithelioma. Ultrastructurally, one reticular myoepithelioma reveals myoepithelial cell differentiation with microfilament aggregates, while the other three examples are composed of modified myoepithelial cells displaying widened intercellular spaces, prominent synthesis of extracellular glycosaminoglycans, distinct basal lamina development, and obvious accumulations of cytoplasmic intermediate filaments. In electron micrographs, the modified myoepithelial cells of the plasmacytoid variant closely resemble the tumour cells in the reticular form. Three cases had expression of both glial fibrillary acid protein (GFAP) and vimentin, but only one of the myoepitheliomas contained muscle-specific actin. At least focally, each of the cases exhibited a considerable spectrum of cytokeratin filaments. Using double-labeled immunofluorescent microscopy of one reticular variant and the plasmacytoid myoepithelioma, there was individual tumour cell co-expression of GFAP and vimentin focally in the plasmacytoid myoepithelioma, but co-expression of cytokeratins 13, 16 and GFAP were not noted in either case. As expected, co-expression of high- and low-molecular weight cytokeratin filaments was widespread in both myoepitheliomas. Most described myoepitheliomas have a solid growth pattern and are composed of spindle and plasmacytoid cells, but based on cytological features and growth patterns in this series, it is apparent that polygonal-shaped cells with novel architecture can occur in myoepitheliomas. The results also indicate the close relationship between pleomorphic adenoma and such variants of myoepithelioma.

Actins↗

PubMed1988

Warthin's tumor: an ultrastructural and immunohistochemical study of basilar epithelium.

The cellular characteristics of the basilar epithelium in Warthin's tumor have had limited investigation. Ultrastructural examination of basal cells in 9 Warthin's tumors reveals that in addition to numerous mitochondria these cells possess a rich complement of tonofilaments. However, in three examples there are a proportion of these tonofilament-rich cells that have a narrow band of microfilaments in the peripheral cytoplasm adjacent to the basal lamina. Frozen sections of Warthin's tumor and normal salivary glands, doubly labeled with rhodamine-phalloidin for actin and monoclonal antibody 312C8-1 for cytokeratin 14, show that normal myoepithelial cells of acini and intercalated ducts have both of these filaments, as do a proportion of basal cells in the tumor. There are distinct differences in the cytokeratin polypeptide complement between normal luminal and myoepithelial cells as well as between luminal and basal cells in Warthin's tumor. Differences occur in the cytokeratin profiles between the luminal and basal cells of Warthin's tumor and comparable cells in the normal gland; however, there continue to be some similarities in the cytokeratin polypeptides of myoepithelium and the basal cells of normal salivary ducts and the basal cells of Warthin's tumor. These findings show that basal cells in Warthin's tumor are a mixed population with some capable of differentiating as myoepithelial-like cells, and that this tumor could arise from any level of the normal salivary gland duct system.

Adenolymphoma↗

PubMed1988

CAPD in elderly patients with cardiovascular risk factors.

Twenty-nine elderly patients (greater than 70 years) on CAPD treatment were compared with 30 younger patients (less than 55 years). Biochemical parameters did not differ between the two groups, apart from blood sugar which was higher in the older patient group. Ultrafiltration rates were almost identical. CAPD-specific complications also did not differ in the two patient groups. Arterial hypertension was well-controlled on CAPD and the proportion of patients requiring antihypertensives fell significantly. 8% of the old patients and 52% of the young patients required antihypertensive medication after 12 months of therapy compared to 38% and 81% before commencement of CAPD. Improvement of hemodynamic parameters was especially pronounced in older patients, who had cardiac risk factors in a high percentage of cases. Age and cardiac risk factors had the highest impact on the outcome, thus explaining the higher mortality in the older patient group. Older patients with renal insufficiency can be treated with CAPD leading to equally good results as those documented for younger patients.

Actuarial Analysis↗

PubMed1981