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101.
Canonical transient receptor potential channel 4 (TRPC4) co-localizes with the scaffolding protein ZO-1 in human fetal astrocytes in culture 总被引:4,自引:0,他引:4
Members of the mammalian transient receptor potential (TRP) family form cation-permeable channels at the plasma membrane implicated in capacitative calcium influx after activation by either second-messenger-mediated pathways or store depletion, or both. This study shows that with the use of RT-PCR, Western blotting, and immunohistochemistry, resting astrocytes express TRPC4 at the cell membrane, particularly at sites of cell-to-cell contact. By confocal imaging and immunoelectron microscopy, we detected co-localization of TRPC4 with the scaffolding protein zonula occludens 1 (ZO-1), and demonstrated that immunoprecipitation with antibodies to ZO-1 brought down TRPC4, and vice-versa. It has been proposed that the targeting of TRPC4 to the cell membrane is dependent on the interaction of the C-terminal TRL motif with PDZ domains. Using transfection of astrocytes with myc-tagged TRPC4 or TRL-motif truncated TRPC4 (deltaTRL), we found that deltaTRL localized predominantly to a juxtanuclear compartment, whereas the wild-type protein showed cell surface distribution. Deletion of the TRL motif also reduced plasma membrane expression as assessed by cell surface biotinylation experiments. Using GST fusion proteins, we found that TRPC4 interacted with the PDZ1 domain of ZO-1 and that this was also dependent on the TRL motif. Thus, our data demonstrate that the PDZ-interacting domain of TRPC4 controls its cell surface localization. These data implicate TRPC4 in the regulation of calcium homeostasis in astrocytes, particularly as part of a signaling complex that forms at junctional sites between astrocytes. 相似文献
102.
Hombach S Janssen-Bienhold U Söhl G Schubert T Büssow H Ott T Weiler R Willecke K 《The European journal of neuroscience》2004,19(10):2633-2640
Horizontal cells are interneurons of the vertebrate retina that exhibit strong electrical and tracer coupling but the identity of the channel-forming connexins has remained elusive. Here we show that horizontal cells of the mouse retina express connexin57 (Cx57). We have generated Cx57-deficient mice by replacing the Cx57 coding region with a lacZ reporter gene, expressed under control of the endogenous Cx57 promoter. These mice were fertile and showed no obvious anatomical or behavioural abnormalities. Cx57 mRNA was expressed in the retina of wild-type littermates but was absent from the retina of Cx57-deficient mice. Previously reported results that the Cx57 gene was very weakly expressed in several other mouse tissues turned out to be unspecific. Cx57 mRNA is abundantly expressed in the retina and weakly in the thymus of adult mice but absent in all other adult tissues tested, including brain. Furthermore, Cx57 is expressed in embryonic kidney at E16.5 to E18.5 days post-conception, as indicated by the pattern of lacZ expression. Within the retina, lacZ signals were assigned exclusively to horizontal cells based on co-localization with cell-type-specific marker proteins. Microinjection of Neurobiotin into horizontal cells of isolated retinae revealed less than 1% of tracer coupling in Cx57-deficient retinae compared with wild-type controls. Cx57 is the first connexin identified in mammalian horizontal cells and the first connexin whose expression is apparently restricted to only one type of neuron. 相似文献
103.
We examined the cholinergic effects on epileptiform discharge generation in immature (postnatal days 10-20) rat neocortex. Evoked and spontaneous field potentials were recorded from the deep layers of neocortical slices during GABA(A) receptor blockade by bicuculline methiodide (BMI, 50 microM). The anticholinesterase eserine (10 microM) as well as the ACh-analog carbamylcholine chloride (CCh, 25 microM) decreased the amplitude and duration of evoked field potentials and in parallel, increased significantly the rate of occurrence of spontaneous discharges. These effects were reversed by the muscarinic antagonist atropine (2.5 microM, n = 20), but not by the nicotinic receptor antagonist hexamethonium (50 microM, n = 3). The M1 subtype-selective muscarinic antagonist pirenzepine (1 microM, n = 12) blocked spontaneous discharges in 8/12 slices, while muscarinic antagonists of the M2 (AFDX 116 n = 4), M3 (4-DAMP n = 4) and M4 (gallamine n = 5, tropicamide n = 6) type, all at 1 microM, only reduced their frequency. CCh-induced spontaneous discharges were blocked by the combination of the glutamate receptor antagonists AP5 and CNQX (both at 10 microM; n = 11). Gap junction blockers abolished them (halothane, n = 7) or reduced their frequency by 65% (carbenoxolone, n = 8). Inhibiting Ca2+ release from intracellular stores by dantrolene (100 microM, n = 5) or thapsigargin (1 microM, n = 5) also depressed their frequencies by 55-65%. By contrast, their rates were not altered by perfusion with high Ca2+ (7 mM; n = 6) medium, a manipulation suppressing polysynaptic connections. These findings demonstrate that activation of muscarinic receptors, notably of the M1 type, in immature rat neocortex facilitates the generation of glutamatergic epileptiform discharges. These discharges are strongly inhibited by gap junction blockers, and are also partly mediated by the, presumably muscarinic receptor-dependent, mobilization of intracellular calcium. 相似文献
104.
Type 1 nitrergic (ND1) cells of the rabbit retina: comparison with other axon-bearing amacrine cells
Vaney DI 《The Journal of comparative neurology》2004,474(1):149-171
NADPH diaphorase (NADPHd) histochemistry labels two types of nitrergic amacrine cells in the rabbit retina. Both the large ND1 cells and the small ND2 cells stratify in the middle of the inner plexiform layer, and their overlapping processes produce a dense plexus, which makes it difficult to trace the morphology of single cells. The complete morphology of the ND1 amacrine cells has been revealed by injecting Neurobiotin into large round somata in the inner nuclear layer, which resulted in the labelling of amacrine cells whose proximal morphology and stratification matched those of the ND1 cells stained by NADPHd histochemistry. The Neurobiotin-injected ND1 cells showed strong homologous tracer coupling to surrounding ND1 cells, and double-labelling experiments confirmed that these coupled cells showed NADPHd reactivity. The ND1 amacrine cells branch in stratum 3 of the inner plexiform layer, where they produce a sparsely branched dendritic tree of 400-600 microm diameter in ventral peripheral retina. In addition, each cell gives rise to several fine beaded processes, which arise either from a side branch of the dendritic tree or from the tapering of a distal dendrite. These axon-like processes branch successively within the vicinity of the dendritic field before extending, with little or no further branching, for 3-5 mm from the soma in ventral peripheral retina. Consequently, these cells may span one-third of the visual field of each eye, and their spatial extent appears to be greater than that of most other types of axon-bearing amacrine cells injected with Neurobiotin in this study. The morphology and tracer-coupling pattern of the ND1 cells are compared with those of confirmed type 1 catecholaminergic cells, a presumptive type 2 catecholaminergic cell, the type 1 polyaxonal cells, the long-range amacrine cells, a novel type of axon-bearing cell that also branches in stratum 3, and a type of displaced amacrine cell that may correspond to the type 2 polyaxonal cell. 相似文献
105.
Changes in the gap junctional coupling and maturation of voltage-activated Na(+) currents during regeneration of newt retinas were examined by whole-cell patch-clamping in slice preparations. Progenitor cells in regenerating retinas did not exhibit Na(+) currents but showed prominent electrical and tracer couplings. Cells identified by LY-fills were typically slender. Na(+) currents were detected in premature ganglion cells with round somata in the 'intermediate-II' regenerating retina. No electrical and tracer couplings were observed between these cells. Mature ganglion cells did not exhibit electrical coupling, but showed tracer coupling. On average, the maximum Na(+) current amplitude recorded from premature ganglion cells was roughly 2.5-fold smaller than that of mature ganglion cells. In addition, the activation threshold of the Na(+) current was nearly 11 mV more positive than that of mature cells. We provide morphological and physiological evidence showing that loss of gap junctions between progenitor cells is associated with ganglion cell differentiation during retinal regeneration and that new gap junctions are recreated between mature ganglion cells. Also we provide evidence suggesting that the loss of gap junctions correlates with the appearance of voltage-activated Na(+) currents in ganglion cells. 相似文献
106.
Frisch C Theis M De Souza Silva MA Dere E Söhl G Teubner B Namestkova K Willecke K Huston JP 《The European journal of neuroscience》2003,18(8):2313-2318
Gap junctions mediate communication between many cell types in the brain. Gap junction channels are composed of membrane-spanning connexin (Cx) proteins, allowing the cell-to-cell passage of small ions and metabolites. Cx43 is the main constituent of the brain-spanning astrocytic gap junctional network, controlling activity-related changes in ion and glutamate concentrations as well as metabolic processes. In astrocytes, deletion of Cx43-coding DNA led to attenuated gap junctional coupling and impaired propagation of calcium waves, known to influence neuronal activity. Investigation of the role of Cx43 in behaviour has been impossible so far, due to postnatal lethality of its general deletion. Recently, we have shown that deletion of Cx30, which is also expressed by astrocytes, affects exploration, emotionality, and neurochemistry in the mouse. In the present study, we investigated the effects of the astrocyte-directed inactivation of Cx43 on mouse behaviour and brain neurochemistry. Deletion of Cx43 in astrocytes increased exploratory activity without influencing habituation. In the open field, but not in the elevated plus-maze, an anxiolytic-like effect was observed. Rotarod performance was initially impaired, but reached control level after further training. In the water maze, Cx43 deficient mice showed a steeper learning course, although final performance was similar between groups. Cx43 inactivation in astrocytes increased acetylcholine content in the frontal cortex of water maze-trained animals. Results are discussed in terms of altered communication between astrocytes and neurons, possible compensation processes, and differential effects of Cx30- and astrocyte-specific Cx43 deletion. 相似文献
107.
Migration of leukocytes across endothelial junctions: some concepts and controversies 总被引:6,自引:0,他引:6
Muller WA 《Microcirculation (New York, N.Y. : 1994)》2001,8(3):181-193
This article is not meant to be a comprehensive review of leukocyte migration or endothelial cell junctions. Rather, I have chosen some aspects of inflammation that might be of general interest to vascular biologists and have focused on the structural and molecular elements of the endothelial junction involved in these processes. These are all active (and some controversial) areas of investigation. I have tried to objectively present both sides of any controversies, while stating at the end the general consensus of the field. 相似文献
108.
Klaus Franke 《European archives of oto-rhino-laryngology》1978,221(3):157-162
Summary Replicas of the freeze fractured spiral limbus are studied in chinchillas. Zonulae occludentes are demonstrated between the interdental cells and the inner sulcus cells; gap junctions are described connecting interdental cells and inner sulcus cells to one another and they are found between the perilymphatic cells in the spiral limbus. 相似文献
109.
R. Walker R. W. Kentridge J. M. Findlay 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1995,103(2):294-310
In a series of experiments we examined the effects of the endogenous orienting of visual attention on human saccade latency. Three separate manipulations were performed: the orienting of visual attention, the prior offset of fixation (gap paradigm) and the bilateral presentation of saccade targets. Each of these manipulations was shown to make an independent contribution to saccade latency. In experiments 1 and 2 subjects were instructed to orient their attention covertly to a location by a verbal pre-cue; targets could appear in the attended hemifield (valid) or in the non-attended hemifield (invalid) together with a no-instruction (neutral) condition. Saccades were made under fixation gap and overlap conditions, to either single targets or two bilaterally presented targets which appeared at equal and opposite eccentricities in both hemifields. The results showed a large increase (cost) of saccade latency to invalid targets and a small non-significant decrease (benefit) of saccade latency to valid targets. The cost associated with invalid targets replicates the meridian crossing effect shown in manual reaction time experiments and is consistent with the hemifield inhibition and premotor models of attentional orienting. The use of a gap procedure produced a generalised facilitation of saccade latency, which was not modified by the prior orienting of visual attention. The magnitude of the gap effect was similar for saccades made to attended and non-attended stimulis. This suggests that the gap effect may be due to ocular motor disengagement, or a warning signal effect, rather than to the prior disengagement of visual attention. When two targets were presented simultaneously, one in each hemifield, saccade latency was slowed compared with the single target condition. The magnitude of this slowing was unaffected by the prior orienting of visual attention or by the fixation condition. The slowing was examined in more detail in experiment 3, by presenting targets with brief offset delays. The latency increase was maximal if the two targets were presented simultaneously and decreased if the distractor appeared at short intervals (20–80 ms) before or after the saccade target onset. If the non-attended stimulus was presented at greater intervals (160, 240 ms) before the saccade target, then a facilitation effect was observed. This demonstrates that the onset of a distractor in the non-attended hemifield can have both an inhibitory and a facilitatory effect on a saccade production. 相似文献
110.
目的:研究生长激素(GH)对脓毒症大鼠肠黏膜屏障功能的影响。方法:将72只大鼠随机分对照组、脓毒症组、脓毒症加GH组,再将各组随机分为空肠组、回肠组和结肠组。空肠组大鼠取Treitz韧带处行空肠置管,距离Treitz韧带25 cm处造口;回肠组自回盲部向上25 cm处置管,末端回肠造口;结肠组行盲肠置管。各组分别于肠道置管造口灌入甘露醇/乳果糖(L/M),收集6 h全部尿液,采用高效液相色谱分析法(HPLC)测定尿L/M值。24 h后处死大鼠,分别取部分空肠、回肠、结肠肠管行体外肠黏膜通透性检测,于透射电镜观察肠上皮细胞间紧密连接(TJ)的超微结构改变。结果:脓毒症组大鼠肠黏膜TJ间隙增宽,肠道通透性增加,且回肠组更加明显;脓毒症加GH组肠黏膜TJ损伤和肠黏膜通透性的增加有所减轻。结论:GH能减轻脓毒症大鼠肠黏膜TJ损伤,改善肠黏膜屏障功能。 相似文献