Single Na+ channel currents observed in cultured rat muscle cells

The voltage- and time-dependent conductance of membrane Na+ channels is responsible for the propagation of action potentials in nerve and muscle cells. In voltage-step-clamp experiments on neurone preparations containing 10(4)-10(7) Na+ channels the membrane conductance shows smooth variations in time, but analysis of fluctuations and other eivdence suggest that the underlying single-channel conductance changes are stochastic, rapid transitions between 'closed' and 'open' states as seen in other channel types. We report here the first observations of currents through individual Na+ channels under physiological conditions using an improved version of the extracellular patch-clamp technique on cultured rat muscle cells. Our observations support earlier inferences about channel gating and show a single-channel conductance of approximately 18 pS.     

Amyloid beta-peptide is produced by cultured cells during normal metabolism.

Alzheimer's disease is characterized by the extracellular deposition in the brain and its blood vessels of insoluble aggregates of the amyloid beta-peptide (A beta), a fragment, of about 40 amino acids in length, of the integral membrane protein beta-amyloid precursor protein (beta-APP). The mechanism of extracellular accumulation of A beta in brain is unknown and no simple in vitro or in vivo model systems that produce extracellular A beta have been described. We report here the unexpected identification of the 4K (M(r) 4,000) A beta and a truncated form of A beta (approximately 3K) in media from cultures of primary cells and untransfected and beta-APP-transfected cell lines grown under normal conditions. These peptides were immunoprecipitated readily from culture medium by A beta-specific antibodies and their identities confirmed by sequencing. The concept that pathological processes are responsible for the production of A beta must not be reassessed in light of the observation that A beta is produced in soluble form in vitro and in vivo during normal cellular metabolism. Further, these findings provide the basis for using simple cell culture systems to identify drugs that block the formation or release of A beta, the primary protein constituent of the senile plaques of Alzheimer's disease.     

束骨姜黄化学成分及其乙酰胆碱酯酶抑制活性

采用硅胶层析、反相硅胶中压柱层析、高效液相等色谱技术对姜科姜黄属束骨姜黄(Curcuma xanthorrhiza Roxb.)根茎中的低极性化学成分进行了分离纯化,并通过MS和NMR等波谱技术确定了化合物结构,分离纯化化合物6个,分别鉴定为蓬莪术环氧酮(Ⅰ)、β 谷甾醇(Ⅱ)、愈创木内酯Guai-1(10),3,5,7(11),8-pentaen-2-on-11,8-olide(Ⅲ)、郁金二酮(Ⅳ)、莪术双环烯酮(Ⅴ)、花侧柏烯(Ⅵ)。化合物Ⅲ、Ⅵ为首次从该科植物中分离得到,化合物Ⅳ、Ⅴ为首次从该种中分离得到。对所分离获得化合物进行了乙酰胆碱酯酶抑制活性测定,其中化合物Ⅳ、Ⅵ具有活性,化合物Ⅳ的TLC生物自显影最小抑制量为95μg。     

Desensitisation of cultured glial cells to epidermal growth factor by receptor down-regulation.

Epidermal growth factor (EGF), which can be purified from the mouse submaxillary gland or from pregnant human urine, is a potent multiplication-stimulating factor for several types of cultured cells, including human fibroblasts and glial cells. The molecule binds with high affinity and saturation kinetics to a cell-surface receptor, is subsequently internalised and finally degraded. The binding event is accompanied by a reduction in the number of EGF receptors. This phenomenon--'receptor down-regulation'--has been demonstrated with several hormones and may be a general principle for the modulation of binding groups on the outer cell surface. Further, it has been proposed that receptor loss acts to regulate the cellular response to the binding ligand. The present study provides direct experimental support for this hypothesis. It demonstrates that down-regulation of EGF receptors on glial cells causes desensitisation of the mitogenic response of these cells to subsequent stimulation with EGF.     

豚鼠离体小肠电活动与机械收缩

以小肠电活动和环肌张力、纵肌张力为指标，用同步记录的方法研究了豚鼠离体小肠电活动与环肌张力、纵肌张力之间的关系，结果表明：（１）豚鼠离体小肠的电活动包括慢波与峰波；（２）豚鼠离体小肠始终存在着节律性张力活动，其环肌收缩与纵肌收缩的关系表现为拮抗收缩、共同收缩、交互抑制等形式；（３）峰波可增加收缩力，峰波的个数、振幅与小肠张力呈正变关系，尤其与环肌收缩的对应关系更为显著．（４）慢波可触发收缩，尤其是纵肌收缩．在没有峰波仅有慢波时，亦可有收缩活动甚至活跃的收缩活动．     

当归对吊尾大鼠比目鱼肌收缩功能的影响

探讨当归对吊尾14天大鼠比目鱼肌(SOL)收缩功能的影响及可能的作用机制。以尾部悬吊法建立大鼠废用性肌萎缩模型,将24只雌性SD大鼠分为正常组(CON),吊尾组(TS)和灌胃当归组(TS+Ang)。用PowerLab系统测定比目鱼肌等长收缩与强直收缩最大张力;定磷法测定Ca2+-ATP酶活性。结果显示:1 TS组肌肉湿重(MWW)和肌肉湿重/体重(MWW/BW)比CON组显著降低,TS+Ang组肌肉湿重升高了17%(P0.05),而肌肉湿重/体重不具统计学意义;2 TS组等长收缩最大张力(Pt)和强直收缩最大张力(Po)比CON组均显著降低;与TS组相比,TS+Ang组Pt值和Po值分别增加91%和49%(P0.01);3与CON组相比,TS组等长收缩最大张力达到一半的时间(TP50),达到等长收缩最大张力的时间(TPT)以及从最大张力峰值到舒张50%(RT50)和75%(RT75)的时间均显著缩短;与TS组相比,灌胃当归组分别增加109%,51%,57%和76%(P0.01);4吊尾组肌浆网Ca2+-ATP酶活性显著升高,灌胃当归后,Ca2+-ATP酶活性降低10%(P0.05)。结果说明:当归能有效缓解吊尾造成的肌肉收缩张力的下降和时程的缩短,当归对抗吊尾引起的比目鱼肌Ca2+-ATP酶活性的升高可能是其抗废用性肌萎缩的重要机制之一。