Enhancement of GABAA Receptor-Mediated Inhibitory Postsynaptic Currents Induced by "Partial Oxygen-Glucose Deprivation

下载PDF阅读器"氧糖剥夺"模型作为研究脑缺血的离体模型被广泛使用,该模型模拟了局灶性脑缺血的主要病理变化.然而在缺血病灶核心区与正常脑组织之间称为缺血半暗带的区域,脑血流也有程度不一的降低.为了模拟这种病理变化,发展了一种"不完全氧糖剥夺"的离体脑片模型,该模型满足两个条件,灌流液里氧气部分剥夺而葡萄糖含量降低;"氧糖剥夺"可以导致谷氨酸介导的兴奋性毒性,从而引起神经细胞的坏死.而A型γ-氨基丁酸受体(GABAAR)介导的神经元抑制性活动可以对抗谷氨酸引起的兴奋性毒性,因此近年来引起广泛的研究兴趣.而谷氨酸受体和γ-氨基丁酸受体功能在缺血半暗带是否有改变尚不得而知.因此本文采用海马脑片全细胞膜片钳的记录方法,研究"不完全氧糖剥夺"对海马CA1区神经元的A型γ-氨基丁酸受体介导的抑制性突触后膜电流(IPSCs)的影响.研究发现"不完全氧糖剥夺"使GABAAR介导的IPSCs的峰值增加而衰减时程延长.进一步研究发现该电流的峰值增加是由于GABAAR-氯离子通道的电导增加所致,而与氯离子的反转电位变化无关.这些发现提示在脑缺血的缺血半暗带区域GABAAR介导的神经元抑制性活动可能是增强的,这可能是神经元面对缺血状态产生自我保护的一种内稳态机制.

Transport of anti-sperm monoclonal IGA and IGC into murine male and female genital tracts from blood - Effect of sex hormones

Ab levels in the genital tract may be important in fertility and in preventing sexually transmitted diseases, In this study, I-125-labeled polymer or monomer mAb IgA (C4pIgA or C4mIgA) and IgC2b (C4IgC) to murine lactate dehydrogenase C4 and a polymer mAb IgA (npIgA) not cross-reacting with mouse sperm were intravenously injected into BALB/c mice, and the relative distribution of these Abs was determined. Polymer IgA was transported much more efficiently into the genital tract, trachea, and duodenum of both sexes than C4IgG and C4 mIgA (p < 0.01), The transport of polymer IgA (C4pIgA and npIgA) into the male genital tract greatly increased following orchiectomy (p < 0.01); this change was not affected by testosterone, suggesting that the unknown regulatory factor(s) from the testis may suppress polymer IgA transport, However, the transport of polymer IgA into female genital tissues was significantly decreased by ovariectomy (p < 0.01); this decline can be rectified by P-estradiol but not progesterone treatment, suggesting that estradiol may stimulate polymer IgA transport, Furthermore, the transport of C4IgG into tissues of the Fallopian tubes and the uterus was significantly decreased by treatment with progesterone (p < 0.01). Together, these findings indicate that serum polymer IgA can be transported selectively into the genital tracts of both sexes, that this transport is strongly under the control of gonads, and that transport of Ige into the Fallopian tubes and uterus is downregulated by progesterone.

Independent Transport and Sorting of Functionally Distinct Protein Families in Tetrahymena thermophila Dense Core Secretory Granules

Dense core granules (DCGs) in Tetrahymena thermophila contain two protein classes. Proteins in the first class, called granule lattice (Grl), coassemble to form a crystalline lattice within the granule lumen. Lattice expansion acts as a propulsive mechanism during DCG release, and Grl proteins are essential for efficient exocytosis. The second protein class, defined by a C-terminal beta/gamma-crystallin domain, is poorly understood. Here, we have analyzed the function and sorting of Grt1p (granule tip), which was previously identified as an abundant protein in this family. Cells lacking all copies of GRT1, together with the closely related GRT2, accumulate wild-type levels of docked DCGs. Unlike cells disrupted in any of the major GRL genes, Delta GRT1 Delta GRT2 cells show no defect in secretion, indicating that neither exocytic fusion nor core expansion depends on GRT1. These results suggest that Grl protein sorting to DCGs is independent of Grt proteins. Consistent with this, the granule core lattice in Delta GRT1 Delta GRT2 cells appears identical to that in wild-type cells by electron microscopy, and the only biochemical component visibly absent is Grt1p itself. Moreover, gel filtration showed that Grl and Grt proteins in cell homogenates exist in nonoverlapping complexes, and affinity-isolated Grt1p complexes do not contain Grl proteins. These data demonstrate that two major classes of proteins in Tetrahymena DCGs are likely to be independently transported during DCG biosynthesis and play distinct roles in granule function. The role of Grt1p may primarily be postexocytic; consistent with this idea, DCG contents from Delta GRT1 Delta GRT2 cells appear less adhesive than those from the wild type.

In vivo studies on the toxic effects of microcystins on mitochondrial electron transport chain and ion regulation in liver and heart of rabbit

This study examined the toxic effects of microcystins on mitochondria of liver and heart of rabbit in vivo. Rabbits were injected i.p. with extracted microcystins (mainly MC-RR and -LR) at two doses, 12.5 and 50 MCLReq. mu g/kg bw, and the changes in mitochondria of liver and heart were studied at 1, 3,12, 24 and 48 h after injection. MCs induced damage of mitochondrial morphology and lipid peroxidation in both liver and heart. MCs influenced respiratory activity through inhibiting NADH dehydrogenase and enhancing succinate dehydrogenase (SDH). MCs altered Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities of mitochondria and consequently disrupted ionic homeostasis, which might be partly responsible for the loss of mitochondrial membrane potential (MMP). MCs were highly toxic to mitochondria with more serious damage in liver than in heart. Damage of mitochondria showed reduction at 48 h in the low dose group, suggesting that the low dose of MCs might have stimulated a compensatory response in the rabbits. (C) 2008 Elsevier Inc. All rights reserved.

Transport-determined early growth and development of jack mackerel Trachurus japonicus juveniles immigrating into Sagami Bay, Japan

Oceanographic conditions and transport processes are often critical factors that affect the early growth, survival and recruitment of marine fishes. Sagittal otoliths were analysed to determine age and early growth for 381 jack mackerel (Trachurus japonicus) juveniles from Sagami Bay on the Pacific coast of Japan. Two separate hatching periods ( December and February-March) were identified. They originated from the spawning grounds in the East China Sea. Early growth and developmental rates of December-hatching fish were lower than those for February-March-hatching fish. It is likely that these differences were determined in the Kuroshio Current during transport from the spawning grounds to Sagami Bay, and the lower December water temperatures in the bay. Origin and hatch dates of juveniles in Sagami Bay were in contrast to previous research on Fukawa Bay, where April-or-later-hatching fish from spawning grounds in the coastal waters of southern Japan constituted about half of the juvenile population. Management of these two jack mackerel stocks needs to consider these differences in hatch date composition and spawning origins, as these differences could affect early growth and subsequent mortality.

Rashba electron transport in one-dimensional quantum waveguides

The properties of Rashba wave function in the planar one-dimensional waveguide are studied, and the following results are obtained. Due to the Rashba effect, the plane waves of electron with the energy E divide into two kinds of waves with the wave vectors k(1)=k(0)+k(delta) and k(2)=k(0)-k(delta), where k(delta) is proportional to the Rashba coefficient, and their spin orientations are +pi/2 (spin up) and -pi/2 (spin down) with respect to the circuit, respectively. If there is gate or ferromagnetic contact in the circuit, the Rashba wave function becomes standing wave form exp(+/- ik(delta)l)sin[k(0)(l-L)], where L is the position coordinate of the gate or contact. Unlike the electron without considering the spin, the phase of the Rashba plane or standing wave function depends on the direction angle theta of the circuit. The travel velocity of the Rashba waves with the wave vector k(1) or k(2) are the same hk(0)/m*. The boundary conditions of the Rashba wave functions at the intersection of circuits are given from the continuity of wave functions and the conservation of current density. Using the boundary conditions of Rashba wave functions we study the transmission and reflection probabilities of Rashba electron moving in several structures, and find the interference effects of the two Rashba waves with different wave vectors caused by ferromagnetic contact or the gate. Lastly we derive the general theory of multiple branches structure. The theory can be used to design various spin polarized devices.

Quantum Mechanical Study on Tunnelling and Ballistic Transport of Nanometer Si MOSFETs

Using self-consistent calculations of million-atom Schrodinger-Poisson equations, we investigate the I-V characteristics of tunnelling and ballistic transport of nanometer metal oxide semiconductor field effect transistors (MOSFET) based on a full 3-D quantum mechanical simulation under nonequilibtium condition. Atomistic empirical pseudopotentials are used to describe the device Hamiltonian and the underlying bulk band structure. We find that the ballistic transport dominates the I-V characteristics, whereas the effects of tunnelling cannot be neglected with the maximal value up to 0.8mA/mu m when the channel length of MOSFET scales down to 25 nm. The effects of tunnelling transport lower the threshold voltage V-t. The ballistic current based on fully 3-D quantum mechanical simulation is relatively large and has small on-off ratio compared with results derived from the calculation methods of Luo et al.

Interference in transport through double barriers in interacting quantum wires

We investigate interference effects of the backscattering current through a double-barrier structure in an interacting quantum wire attached to noninteracting leads. Depending on the interaction strength and the location of the barriers, the backscattering current exhibits different oscillation and scaling characteristics with the applied voltage in the strong and weak interaction cases. However, in both cases, the oscillation behaviors of the backscattering current are mainly determined by the quantum mechanical interference due to the existence of the double barriers.