家蝇GABA受体抑制剂的药效团模型构建

选取具有较高体外抑制活性且结构差异较大的四类GABA受体抑制剂作为化合物集,利用Catalyst软件,经分子结构搭建、构象分析、药效团识别,构建出了家蝇GABA受体抑制剂的药效团模型.经分析、筛选得到含有一个芳环中心、一个脂肪性疏水中心和两个氢键受体的具有较好预测能力(RMS=0.766449,Correl=0.905422,Weight=1.87642,Config=13.7434)的药效团模型.该模型的构建对揭示配体与GABA受体作用的药效模式及设计新型GABA受体抑制剂具有重要指导意义.     

Sequence and functional expression of the GABA A receptor shows a ligand-gated receptor super-family

Amino-acid sequences derived from complementary DNAs encoding the alpha- and beta-subunits of the GABA/benzodiazepine receptor from bovine brain show homology with other ligand-gated receptor subunits, suggesting that there is a super-family of ion-channel-containing receptors. Co-expression of the in vitro-generated alpha-subunit and beta-subunit RNAs in Xenopus oocytes produces a functional receptor and ion channel with the pharmacological properties characteristic of the GABAA receptor.     

Intracellular calcium stores regulate activity-dependent neuropeptide release from dendrites

Information in neurons flows from synapses, through the dendrites and cell body (soma), and, finally, along the axon as spikes of electrical activity that will ultimately release neurotransmitters from the nerve terminals. However, the dendrites of many neurons also have a secretory role, transmitting information back to afferent nerve terminals. In some central nervous system neurons, spikes that originate at the soma can travel along dendrites as well as axons, and may thus elicit secretion from both compartments. Here, we show that in hypothalamic oxytocin neurons, agents that mobilize intracellular Ca(2+) induce oxytocin release from dendrites without increasing the electrical activity of the cell body, and without inducing secretion from the nerve terminals. Conversely, electrical activity in the cell bodies can cause the secretion of oxytocin from nerve terminals with little or no release from the dendrites. Finally, mobilization of intracellular Ca(2+) can also prime the releasable pool of oxytocin in the dendrites. This priming action makes dendritic oxytocin available for release in response to subsequent spike activity. Priming persists for a prolonged period, changing the nature of interactions between oxytocin neurons and their neighbours.     

Intracellular free calcium rise triggers nuclear envelope breakdown in the sea urchin embryo

Cytosolic free calcium has recently been implicated in the regulation of mitosis in plant and animal cells. We have previously found correlations between increases in the levels of intracellular free calcium [Ca2+]i and visible transitions of structure at nuclear envelope breakdown (NEBD) and the onset of anaphase during mitosis in sea urchin embryos and tissue culture cells. To go beyond correlations it is necessary to manipulate [Ca2+]i, and in sea urchin embryos this requires the injection of calcium-chelator buffer solutions as the changes in free calcium in the cell cycle are dependent on intracellular stores. We report here that blocking the increase in [Ca2+]i which just precedes NEBD prevents this from taking place and halts mitosis. Subsequent injections which momentarily increase [Ca2+]i, or a natural recovery of the higher calcium levels, result in NEBD and the successful continuation of mitosis. Similarly, artificially increasing calcium by early injections results in early NEBD. We conclude that the increase in [Ca2+]i preceding NEBD is an essential regulatory step required for entry into mitosis.     

钙离子与钠离子对浆料Zeta电位的影响

用氯化钙和氯化钠调节添加了不同化学助剂的去金属离子浆料电导率,用德国mütek 公司SZP-04型Zeta电位仪检测对比浆料Zeta电位的变化情况,探讨了Na+和Ca2+对浆料Zeta电位的不同影响,并应用Minitab软件对实验测得的结果进行量化分析。结果表明：无机盐离子使浆料Zeta电位绝对值下降,Ca2+对浆料Zeta电位绝对值的降低作用高于Na+。浆料Zeta电位（ζ）随浆料电导率（σ）以及浆料初始Zeta电位值（ζ0）的变化符合数学模型：ζ=-0.388+0988ζ0+0.202lnσ-ζ00.091lnσ（氯化钙调节电导率时）, ζ=-0.806+ 0.960ζ0-0.316lnσ-ζ00.102lnσ（氯化钠调节电导率时）。浆料Zeta电位在等电点附近时,CPAM的助留助滤性能最佳。与Na+相比,Ca2+更容易使造纸系统的Zeta电位值过高甚至达到正值,从而影响浆料的性能。     

Intracellular calcium dependence of transmitter release rates at a fast central synapse

Calcium-triggered fusion of synaptic vesicles and neurotransmitter release are fundamental signalling steps in the central nervous system. It is generally assumed that fast transmitter release is triggered by elevations in intracellular calcium concentration ([Ca2+]i) to at least 100 microM near the sites of vesicle fusion. For synapses in the central nervous system, however, there are no experimental estimates of this local [Ca2+]i signal. Here we show, by using calcium ion uncaging in the large synaptic terminals of the calyx of Held, that step-like elevations to only 10 microM [Ca2+]i induce fast transmitter release, which depletes around 80% of a pool of available vesicles in less than 3 ms. Kinetic analysis of transmitter release rates after [Ca2+]i steps revealed the rate constants for calcium binding and vesicle fusion. These show that transient (around 0.5 ms) local elevations of [Ca2+]i to peak values as low as 25 microM can account for transmitter release during single presynaptic action potentials. The calcium sensors for vesicle fusion are far from saturation at normal release probability. This non-saturation, and the high intracellular calcium cooperativity in triggering vesicle fusion, make fast synaptic transmission very sensitive to modulation by changes in local [Ca2+]i.