4-Aminopyridine and fiber potentials in rat and human hippocampal slices

Cellular and Molecular Life Sciences - Compound fiber action potentials of stratum radiatum afferents in slices from human and rat hippocampus are shown to be prolonged by 4-aminopyridine (4-AP)....     

Immunoglobulin heavy chain binding protein

Pre-B lymphocytes, and hybridomas derived from them, synthesize immunoglobulin heavy (IgH) chain in the absence of light (L) chain. In the Abelson virus transformed line 18-81, which is representative of the pre-B cell stage, we observed that at least some of the H-chains are bound to a protein other than L-chain. Here we show that the protein (which we term immunoglobulin heavy-chain binding protein, BiP) binds non-covalently to free IgH, but not to IgH associated with IgL.     

X-ray structure of phospholipase A2 complexed with a substrate-derived inhibitor

Phospholipases A2 play a part in a number of physiologically important cellular processes such as inflammation, blood platelet aggregation and acute hypersensitivity. These processes are all initiated by the release of arachidonic acid from cell membranes which is catalysed by intracellular phospholipases A2 and followed by conversion of arachidonic acid to prostaglandins, leukotrienes or thromboxanes. An imbalance in the production of these compounds can lead to chronic inflammatory diseases such as rheumatoid arthritis and asthma. Inhibitors of phospholipase A2 might therefore act to reduce the effects of inflammation, so structural information about the binding of phospholipase A2 to its substrates could be helpful in the design of therapeutic drugs. The three-dimensional structure is not known for any intracellular phospholipase A2, but these enzymes share significant sequence homology with secreted phospholipases, for which some of the structures have been determined. Here we report the structure of a complex between an extracellular phospholipase A2 and a competitively inhibiting substrate analogue, which reveals considerable detail about the interaction and suggests a mechanism for catalysis by this enzyme.     

Angiotensin II in the hippocampus. A histochemical and electrophysiological study

Summary The presence of the renin angiotensin system in the hippocampus is shown by immunohistochemistry. Intra- and extra-cellular recordings revealed that angiotensin II and III excite CA 1 pyramidal cells by disinhibition. The effect is antagonized by [Sar¹, Thr⁸]-A II.This work was supported by grant Nos 3.271.78 and 3.396.78 of the Swiss National Science Foundation and research grant HL-24112 from NIH. T. Inagami was a visiting scientist of the Roche Medical Research Foundation.     

Histamine and noradrenaline decrease calcium-activated potassium conductance in hippocampal pyramidal cells

Ample evidence exists for histaminergic and noradrenergic projections to the hippocampus. Both amines exert neurotransmitter or modulator actions on principal neurones in the CA 1 and in the dentate area. A number of mechanisms have been proposed for these actions, including increased potassium conductance, increased chloride conductance and electrogenic pump stimulation, and reduction of the anomalous inward rectification. Action potentials, and particularly bursts of spikes, in CA 1 pyramidal cells, are followed by an afterhyperpolarization (AHP) which consists of two components. The late AHP depends on a calcium-activated potassium conductance gK+ (Ca2+), and has recently been shown to be increased by dopamine. We report here a rapid and reversible decrease of the late AHP component following a burst of sodium spikes or a calcium spike, during perfusion with micromolar concentrations of histamine and noradrenaline. This effect is mediated by H2 receptors and beta-receptors, respectively, and occurred in the absence of changes in the calcium spike. By such a mechanism histamine and noradrenaline can profoundly potentiate the excitatory impact of depolarizing signals.     

The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus)

Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 3x draft genome sequence of 'SunUp' papaya, the first commercial virus-resistant transgenic fruit tree to be sequenced. The papaya genome is three times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease-resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far, may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree-like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit-tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica's distinguishing morpho-physiological, medicinal and nutritional properties.