Ultrastructure of the anterior ventral and anterior medial nuclei of the cat thalamus

Summary Electron microscopical studies of the thalamic AV-AM nuclei substantiated the presence of two main types of neurons, i.e. principal (or relay) cells and Golgi type II interneurons. Characteristic synaptic islands are found in abundance in the AV-AM. Four different types of synaptic terminals have been identified in these islands: RL-boutons = large axonal terminals with round synaptic vesicles; RS-boutons = small axonal terminals with round synaptic vesicles; F₁-boutons = small axonal profiles containing flattened synaptic vesicles, and F₂-profiles interpreted as presynaptic dendrite appendages, bearing pleomorphic vesicles, both belonging to the Golgi type II interneurons. — The synaptic relations were studied in normal preparations and after lesions in the mamillary body, limbic cortex and hippocampus. The specific afferents (RL-boutons) — originating from the medial mamillary nucleus — are presynaptic to both relay cell dendrites and presynaptic dendrite profiles of Golgi type II interneurons, which in turn are presynaptic to the same relay dendrites (synaptic triads). RS-boutons originate mainly from limbic cortex and hippocampus.     

Morphological study of cerebellar transplant cocultivated with cerebral cortical graft in the anterior eye chamber

Summary Morphological organization of Purkinje cells and of molecular layer of the cerebellar cortex cocultivated intraocularly with cerebral cortex for two months was studied. It was found, that while numerous spines on the main dendritic branches of Purkinje cells in single cerebellar grafts were vacant and non-synaptic, dendritic spines of thick Purkinje dendrites in double grafts were covered by large presynaptic bags. The resulting complex synaptic arrangement was strikingly similar although not identical to climbing terminals in normal (in situ) cerebellar cortex. Three distinct types of large presynaptic climbing-fibre like terminals were distinguished: (a) bouton with dense matrix and small round synaptic vesicles, (b) with large round vesicles and (c) containing ovoid synaptic vesicles. The spines of the thin, presumably tertiary dendritic branches were contacted mostly by one parallel axon varicosity, or — as a contrast to normal conditions-by axon terminal, containing ovoid synaptic vesicles. Irrespective of the shape of synaptic vesicles in the presynaptic terminal, all spine-synapses were of asymmetric type; in contrast, synapses on the dendritic shafts were always symmetric.GABA-immunogold reaction has revealed the presence of this inhibitory transmitter in most axon terminals containing ovoid-pleomorphic vesicles within the molecular layer, including those resembling climbing fiber-terminals. This shows a plasticity of the Purkinje cell dendrites to receive non-specific, foreign axons in the absence of specific afferents. Also, the type of synaptic junctions, i.e. whether symmetric or asymmetric, is determined exclusively by the postsynaptic neuron and is independent of the transmitter content of the presynaptic terminal.     

Different kinds of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells. I. Morphometric analysis

Summary An examination of material prepared for conventional electron microscopy has indicated that there are at least four different types of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells in the rat visual cortex. One type of terminal synapses with the initial axon segment and it is derived from the chandelier cell. Because the location and features of these terminals allow them to be readily recognized, chandelier cell terminals were used to determine the extent of morphometric variability that can exist among terminals originating from one cell type. It was found that there is a wide range of mean synaptic vesicle size among chandelier terminals, so that calculated mean vesicle profile diameters for individual terminals can be between 32 and 39 run. Similar ranges of mean synaptic vesicle sizes also exist among populations of the other three axon terminal types. These terminal types are referred to as large, medium-sized, and dense terminals. The large terminals synapse with the cell bodies of layer II/III pyramids and their profiles often measure 1.5 × 0.8 m. The large terminals contain rather loosely packed pleomorphic vesicles and they frequently synapse with a second neuronal element. The medium-sized terminals are smaller, being 1.0 × 0.6–0.8 m in size, and their synaptic vesicles are usually more closely packed than those within the large terminals. The medium-sized terminals are the ones encountered most frequently on the cell bodies of pyramidal cells and they can also occur on the axon hillock and initial axon segment. The dense terminals are usually flattened against the cell body, and they contain rather rounded and closely packed synaptic vesicles, which often seem to be enmeshed in a rather dark cytoplasmic matrix. This matrix and the close packing of the vesicles makes these terminals appear to be more dense than the others. It is now necessary to determine the origins of the large, medium and dense terminals, and to ascertain if they all use GABA as their neurotransmitter.     

Light and electron microscopic analysis of synaptic input from cortical area 17 to the lateral posterior nucleus in cats

The morphology and synaptic organization of the corticothalamic (CT) fibres from area 17 were studied in the lateral posterior nucleus (LP) of the thalamus in cats. Injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHAL) into primary visual cortex labelled a band of CT fibres in the LP with terminal field confined to its lateral division LP1. PHAL-labelled CT axons in the LP1 gave rise to both en passant and terminal boutons. They usually established several synaptic contacts -often in complex glomerulus-like synaptic arrangements-with dendritic shafts of large diameter and presynaptic dendrites containing pleomorphic vesicles. Postsynaptic targets of the PHAL-labelled CT boutons were characterized by postembedding -aminobutyric acid (GABA) immunocytochemistry. It appeared that, in the LP1 of the cat, almost half (44.5%) of the postsynaptic dendrites to CT boutons from area 17 belonged to the GABA-immunopositive interneurons and the majority (41%) of these GABA-immunopositive dendrites were F2 terminals. These results indicate that the CT axons from the striate cortex in the LP of the cat, in addition to a direct excitatory action, exert a powerful feed-forward inhibition on the thalamic principal cells.     

Two types of GABA-containing axon terminals in cerebellar glomeruli of cat: An immunogold-EM study

Summary Immunogold demonstration of GABA was used in ultrathin sections of cerebellar cortex of cat to identify GABA(+) profiles in cerebellar glomeruli. In addition to small, GABA-containing axonal varicosities found at the periphery of all glomeruli, a few complex glomeruli were found to contain a second type of GABA(+) terminal, with a mossy ending appearance. GABA(+) type I axon terminals, which were identified as the axonal arborization of local Golgi cells, contained ovoid, small synaptic vesicles. GABA(+) type II terminals, however, exhibited large, spheroid synaptic vesicles. Experimental evidence is provided that type II GABA(+) mossy like terminals are the endings of nucleocortical fibers.     

Ultrastructural study of ascending projections to the lateral mammillary nucleus of the rat

Summary We examined the synaptic organization of ascending projections from the pars ventralis of the dorsal tegmental nucleus of Gudden (TDV) and the laterodorsal tegmental nucleus to the lateral mammillary nucleus (LM). The LM neuropil consists of terminals containing pleomorphic synaptic vesicles and forming symmetric synaptic contact, and terminals containing round synaptic vesicles and forming asymmetric synaptic contact. They make up 63% and 37%, respectively, of all axodendritic terminals. All axosomatic terminals contain pleomorphic vesicles and make symmetric contact. Following injection of WGA-HRP into the TDV, many anterogradely labeled terminals and retrogradely labeled cells are found in the LM. Labeled terminals contact mainly proximal (more than 2 m diameter) and intermediate (1–2 m diameter) dendrites. Serial ultrathin sections of the LM show that 55% of axosomatic terminals are labeled anterogradely. Following injection of WGA-HRP into the laterodorsal tegmental nucleus, many anterogradely labeled terminals are found in the LM, but no retrogradely labeled cells are present. Labeled terminals contact mainly distal (less than 1 m diameter) and intermediate dendrites as well as somata. In the LM neurons, 46% of axosomatic terminals are labeled anterogradely. All labeled terminals from these nuclei contain pleomorphic vesicles and make symmetric synaptic contact. These results indicate that almost all axosomatic terminals come from the TDV and the laterodorsal tegmental nucleus, which send inhibitory inputs to the lateral mammillary nucleus.     

On the regulation of the expressed L-type calcium channel by cAMP-dependent phosphorylation

The Ca²⁺ channel subunits _1C-a and _1C-b were stably expressed in Chinese hamster ovary (CHO) and human embryonic kidney (HEK) 293 cells. The peak Ba²⁺ current (I _Ba) of these cells was not affected significantly by internal dialysis with 0.1 mM cAMP-dependent protein kinase inhibitor peptide (mPKI), 25 M cAMP-dependent protein kinase catalytic subunit (PKA), or a combination of 25 M PKA and 1 M okadaic acid. The activity of the _1C-b channel subunit expressed stably in HEK 293 cells was depressed by 1 M H 89 and was not increased by superfusion with 5 M forskolin plus 20 M isobutylmethylxanthine (IBMX). The _1C-a·₂·₂/ complex was transiently expressed in HEK 293 cells; it was inhibited by internal dialysis of the cells with 1 M H 89, but was not affected by internal dialysis with mPKI, PKA or microcystin. Internal dialysis of cells expressing the _1C-a·₂·₂/ channel with 10 M PKA did not induce facilitation after a 150-ms prepulse to +50 mV. The Ca²⁺ current (I _Ca) of cardiac myocytes increased threefold during internal dialysis with 5 M PKA or 25 M microcystin and during external superfusion with 0.1 M isoproterenol or 5 M forskolin plus 50 M IBMX. These results indicate that the L-type Ca²⁺ channel expressed is not modulated by cAMP-dependent phosphorylation to the same extent as in native cardiac myocytes.     

The ultrastructure of retinula cell endings in the compound eye of the crayfish

Summary The retinula cell axons entering the synaptic region of the optic lamina in the crayfish form large expanded bag-like terminals which are organized with other neural elements into structural units called cartridges. The cytoplasm of the terminals contains synaptic and coated vesicles, ER cisternae, clusters of tubular elements, and mitochondria. Several mitochondria are often found associated with a single large rod-shaped inclusion present within each terminal. The rod-like formation could be demonstrated in both light and EM material, it is composed of 85–95 Å filaments and averages I m in width and 6.5 m in length.The terminal synaptic contacts are characterized by a bar-shaped presynaptic density and three postsynaptic elements. Some synaptic vesicles appear aligned along the bar density which measures approximately 800 Å in width and 0.75 m in length. Each terminal synapse has three postsynaptic elements which have an electron-dense fringe along their membrane bordering the synaptic cleft. From the planes of section through this contact a composite reconstruction is presented.Also present along the central border of the terminals are numerous small invaginated processes, some of which extend almost to the middle of the terminal. No membrane specializations were found along these processes and they have been tentatively identified as neuronal.     

Untersuchungen zur Bedeutung des β1C/1A-Gehaltes im Serum von Patienten mit sog. „lupoider“ Hepatitis

Zusammenfassung 111 Patienten mit chronischentzündlichen Lebererkrankungen, darunter 13 Kranke mit sog. lupoiden Verlaufsformen (12 Frauen und 1 Mann), wurden auf mögliche Zusammenhänge zwischen dem Auftreten und dem Titer antinucleärer Faktoren (ANF) und der _1C/1A-Globulinkonzentration im Serum untersucht. Die Titer der ANF des lupoiden Kollektivs (N=13) lagen zwischen 1:8 und 1:512. Der Mittelwert der _1A-Globulinkonzentration betrug 91,9±26,8 mg/100 ml. Für die negative Kontrollgruppe ohne ANF (N=98) wurde die _1A-Globulinkonzentration im Mittel mit 91,1±29,92 mg/100 ml bestimmt. Bei einem Korrelationskoeffizienten von 0,0916 bot das Verhalten der C3-Komponente somit keinen Hinweis auf eine besondere immunologische Reaktionsweise sog. lupoider Hepatitiden bzw. Cirrhosen.

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Summary 111 patients suffering from chronic-inflammatory liver disease, including 13 individuals with lupoid hepatitis or cirrhosis (12 female, 1 male), were studied for a possible relationship between the occurrence and the titier of antinuclear factors (ANF) and the concentration of the _1C/1A-globulin in the serum. The titers of the ANF in the lupoid group (N=13) varied between 1:8 and 1:512. The mean value of the _1A-globulin was 91.9±26.8 mg/100 ml. For the ANF-negative group (N=98) the mean value of _1A-globulin was determined as 91.1±29.92 mg/100 ml. The calculated correlation coefficient was 0.0916. Thus, using the content of the C3-component of serum as a parameter there was no evidence of a particular immunologic reactivity of patients with lupoid hepatitis resp. cirrhosis.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Alterations in axons and synapses of olfactory cortex following olfactory bulb lesions in newborn rats

Summary The olfactory cortex of rats is being studied at various survival times following deafferentating olfactory bulb ablation on the day of birth. The neonatal axons and synaptic terminals undergo rapid, flocculent degeneration and fragmentation. Most are not electron-dense and therefore probably not argyrophilic at this particular age of the lesion. The degeneration and removal of debris is far more rapid than in adults, yielding a markedly enlarged extracellular space with a relative absence of glia at the vacated postsynaptic thickenings. Denervated postsynaptic thickenings become occupied by neuronal and nonneuronal profiles and profiles of uncertain origin, singly or in various combinations, or the sites may remain partially vacant. One or more axons with synaptic vesicles often aggregated at the site are commonly involved. Certain terminals form contacts on progressively greater lengths of the thickening until typical synaptic contacts predominate by 14 days survival. The results suggest a competitive reinnervation process and provide a fine structural explanation for the events leading to alterations in this pathway following neonatal deafferentation.This project was supported in part by NIH Research Grants DE 04942, awarded by the National Institute of Dental Research, and Grants NS 09678 and NS 04053 from the National Institute of Neurological and Communicative Disorders and Stroke, PHS/DHEWDr. Westrum is also an affiliate of the Child Development and Mental Retardation Center, University of Washington     

Quantitative morphology and synaptology of cerebellar glomeruli in the rat

Summary Computer-assisted stereological and quantitative morphological approaches were used to analyse cerebellar glomeruli of the simple type in serial ultrathin sections. It was found that, of the total volume (110–200 m³) of the glomeruli studied, 53% was occupied by granule cell dendrites, 34% by mossy terminal and 13% by Golgi axons. None of the four analysed glomeruli contained Golgi cell dendrites. The mossy terminals that were studied received, on the average, 53 granule cell dendrites. All of the dendrites originated from different granule cells and all made synaptic contacts with mossy terminal. However only about 60% of granule cell dendrites made synapses with Golgi axons. The surface of the mossy terminals occupied by synaptic junctions, was found to be 5.4–5.5%. Each granule cell dendrite emitted 3–5 terminal protrusions (dendritic digits). Each digit receives one or more synaptic contact from either the mossy terminal (67% of all digits), or from Golgi axon varicosities (25%). Only about 8% of all digits were contacted synaptically by both types of axonal terminals. All of the dendritic digits that were observed made synaptic connections. Each digit was, on the average, connected by symmetric attachment plaques to 4 neighbouring digits. Three-dimensional reconstructions of mossy terminal and some of contacting granule cell dendrites demonstrated that the dendrites curved around the central mossy terminal and were much longer than expected from earlier Golgi-impregnation studies. In addition to mossy terminals and Golgi axons, an axon terminal of small calibre that contained large, empty, spheroid vesicles were occasionally observed. These terminals, which are most likely the axonal varicosities of ascending parallel fibers, made synaptic contacts exclusively with granule cell dendrites at the periphery of the glomeruli.The results demonstrate that, in the rat cerebellum, there is a high degree of convergence of granule cells at a glomernius (53 to 1); and that there is a rich inhibitory input to about 60% of all granule cell dendrites. It is also shown that the main postsynaptic targets, for both mossy and Golgi axons, are the dendritic digits. The presence of synaptic contacts between parallel-fiber-like varicosities and granule cell dendrites may be an additional source of excitation within the glomerulus.     

Comparison of the Cholinergic System in Neocortical Field Ep in Cats with Strong and Weak Cognitive Abilities

Comparative analysis of the cholinergic system of the neocortex, consisting of the terminals of neurons from the magnocellular basal nuclei and intracortical neurons, in cats with strong and weak abilities to solve abstraction and generalization tasks was performed by isolating subfractions of synaptic membranes and synaptoplasm from light (C) and heavy (D) synaptosomes from associative field Ep and measuring choline acetyltransferase and acetylcholinesterase activities, protein content, and sulfhydryl group concentrations. These experiments showed that all measures were significantly lower in subfractions from C synaptosomes from cats with strong cognitive abilities. This leads to the conclusion that relatively small numbers of cholinergic synapses form in field Ep of the brains of cats with strong cognitive abilities, while their location in the C fraction demonstrates that they correspond to neurons of the magnocellular basal nuclei. The possible physiological significance of the deficiency of cholinergic inputs in field Ep from these nuclei as a correlate of the animal's cognitive ability is discussed. The D subfractions from able cats had significantly higher acetylcholinesterase activity, while choline acetyltransferase activity was not different; this identifies differences between groups of animals in the organization of non-cholinergic acetylcholinesterase-containing synapses in field Ep.     

The effects of indomethacin and verapamil on the shape changes of vascular endothelial cells resulting from exposure to various inflammatory agents

Histamine (300 M), bradykinin (2 M), prostaglandin E₂ (PGE₂) (30 M), or the leukotrienes (LT) C₄ and E₄ (1 M) but not D₄ (1 M) appliedin vitro have been shown to change the shape of endothelial cells lining the guinea pig isolated thoracic inferior vena cava. All caused the formation of inter-endothelial cell gaps. Pre-treatment with either indomethacin (100 M) or verapamil (20 M) reduced the effects of these compounds. It is suggested that indomethacin and verapamil act by reducing the amount of intracellular calcium available for the shortening of contractile protein filaments within endothelial cells.     

Sensitivity to dihydropyridines, ω-conotoxin and noradrenaline reveals multiple high-voltage-activated Ca2+ channels in rat insulinoma and human pancreatic β-cells

High-voltage-activated (HVA) Ba²⁺ currents of rat insulinoma (RINm5F) and human pancreatic -cells were tested for their sensitivity to dihydropyridines (DHPs), -conotoxin (-CgTx) and noradrenaline. In RINm5F cells, block of HVA currents by nimodipine, nitrendipine and nifedipine was voltage- and dose-dependent (apparent K _D<37 nM) and largely incomplete even at saturating doses of DHPs (mean 53%, at 10 M and 0 mV). Analysis of slow tail currents in Bay K 8644-treated cells indicated the existence of Bay K 8644-insensitive channels that turned on at slightly more positive voltages and deactivated more quickly than Bay K 8644-modified channels. DHP Ca²⁺ agonists and antagonists in human -cells had similar features to RINm5F cells except that DHP block was more pronounced (76%, at 10 M and 0 mV) and Bay K 8644 action was more effective, suggesting a higher density of L-type Ca²⁺ channels in these cells. In RINm5F cells, but not in human -cells, DHP-resistant currents were sensitive to -CgTx. The toxin depressed 10–20% of the DHP-resistant currents sparing a residual current (25–35%) with similar voltage-dependent characteristics and Ca²⁺/Ba²⁺ permeability. Noradrenaline (10 M) exhibited different actions on the various HVA current components: (1) it prolonged the activation kinetics of -CgTx-sensitive currents, (2) it depressed by about 20% the size of DHP-sensitive currents, and (3) it had little or no effects on the residual DHP- and -CgTx-resistant current although intracellularly applied guanosine 5-O-(3-thiotriphosphate) (GTP--S) prolonged its activation time course. The first action was clearly voltage-dependent and most evident in RINm5F cells that displayed neuronal-like processes. The second was observed more frequently, was voltage-independent and fully blocked by saturating doses of nifedipine (10 M). Both actions were prevented by intracellular perfusion with guanosine 5-O-(2-thiodiphosphate) (GDP--S). Our data suggest that beside a majority of L-type channels, RINm5F and human pancreatic -cells may express a variable fraction of DHP-insensitive channels that may be involved in the control of insulin secretion during -cell activity.     

Expression of growth factor receptors in injured nervous tissue. I. Axotomy leads to a shift in the cellular distribution of specific beta-nerve growth factor binding in the injured and regenerating PNS

Summary We have studied -nerve growth factor (-NGF) receptor expression in the injured and regenerating chick PNS using [¹²⁵I]-iodinated -NGF as a radioactive probe to map and quantitate autoradiographically thein situ distribution of specific [¹²⁵I] -NGF binding.Two different mechanisms are involved in the reappearance of specific [¹²⁵I] -NGF binding on the normally unlabelled adult peripheral nerves. The anterograde and retrograde axonal transport of -NGF binding sites leads to a rapid but transient accumulation of [¹²⁵I] -NGF binding on both sides of crushed or transected sciatic and brachial nerves. There is a dramatic decrease in the axonal transport of -NGF binding sites, starting 1 day after, nerve injury (1 DPO) and reaching basal levels of 10–20% of the control values at 3 to 10 DPO. Gradual but complete recovery of this axonal transport was noted in the sciatic neurites allowed to regain contact with their peripheral targets. A very different regulation pattern was observed for the local reappearance of specific [¹²⁵I] -NGF binding on the endoneurial Schwann cells throughout the distal part of the axotomized nerve. It was first observed at 4 DPO, becoming maximal at 6 DPO. Reinnervation of the nerve after crush led to a rapid decrease of this specific [¹²⁵I] -NGF binding, which followed a proximo-distal temporal gradient.These results show that axotomy leads to a drastic decrease in the axonal expression of [¹²⁵I] -NGF binding, while causing its appearance on the Schwann cells of the denervated endoneurium. They suggest that these endoneurial cells may become the primary target for -NGF following axotomy and during regeneration.     

Partitioning of Cortical and Deep Cytoskeleton Responses from Transient Magnetic Bead Twisting

We attempted to estimate in living adherent epithelial alveolar cells, the degree of structural and mechanical heterogeneity by considering two individualized cytoskeleton components, i.e., a submembranous cortical cytoskeleton and a deep cytoskeleton (CSK). F-actin structure characterizing each CSK component was visualized from spatial reconstructions at low and high density, respectively, especially in a 10-m-cubic neighborhood including the bead. Specific mechanical properties (Young elastic and viscous modulus E and ) were revealed after partitioning the magnetic twisting cytometry response using a double viscoelastic solid model with asymmetric plastic relaxation. Results show that the cortical CSK response is a faster ( ₁ 0.7s), softer (E₁: 63-109 Pa), moderately viscous (₁: 7-18 Pa s), slightly tensed, and easily damaged structure compared to the deep CSK structure which appears slower (₂ min), stiffer (E₂: 95-204 Pa), highly viscous (₂: 760-1967 Pa s), more tensed, and fully elastic, while exhibiting a larger stress hardening behavior. Adding drug depolymerizing actin filaments decreased predominantly the deep CSK stiffness. By contrast, an agent altering cell–matrix interactions affected essentially the cortical CSK stiffness. We concluded that partitioning the CSK within cortical and deep structures is largely consistent with their respective functional activities. © 2003 Biomedical Engineering Society. PAC2003: 8716Ka, 8716Ac, 8380Lz     

Architecture and synaptic relationships in the intermediolateral nucleus of the thoracic spinal cord of the rat: HRP labelling, catecholamine histochemistry and electron microscopic studies

Summary The organization of the intermediolateral nucleus (IML) of the thoracic spinal cord was examined using glyoxylic acid-induced fluorescence histochemistry, retrograde horseradish peroxidase (HRP) labelling and electron microscopy. In serial sections of T2, it was found that the distribution of catecholamine nerve terminals was intimately related to the neuronal perikarya of IML. Potassium permanganate fixation and 5-hydroxydopamine treatment revealed small dense-cored vesicles in axon varicosities with or without synaptic specializations. A gelatinous region, composed of small diameter dendrites and unmyelinated axons, formed a narrow longitudinal bundle in the centre of the nucleus. The population of the axon varicosities in the IML was 0.17 ± 0.02/m² in 75 nm sections. The average size of the axon varicosities with flat synaptic vesicles was 1.44 ± 0.05 m² and that of varicosities with spherical vesicles was 0.97 ± 0.02 m². After HRP injection into the superior cervical ganglion, ipsilateral IML neurons were labelled in T1–T3 segments of the spinal cord. Axon varicosities with flat and others with spherical synaptic vesicles synapsed on the dendrites labelled by HRP. Among axon varicosities synapsing on the preganglionic sympathetic neurons, 74.8 ± 7.1% at axo-somatic synapses and 46.0 ± 6.7% at synapses on proximal dendrites contained flat synaptic vesicles.     

Mechanism of modulation of single sodium channels from skeletal muscle by the β 1-subunit from rat brain

We studied the molecular mechanism of the rat skeletal muscle -subunit (_I) gating kinetics modulation by the brain ₁-subunit by heterologous expression of single sodium channels from _I and ₁ in Xenopus laevis oocytes. Coexpression of ₁ reduced mean open time at –10 mV to 21% when compared to channels expressed by _I alone. Channels formed by _I exerted multiple openings per depolarization, which occurred in bursts, in contrast to the channels formed by the _I/₁ complex that opened in average only once per depolarizing voltage pulse. Macroscopic current decay (mcd), as evidenced by reconstructed open probability vs. time , was greatly accelerated by ₁, closely resembling mcd of sodium currents from native skeletal muscle. Generally was larger for channels expressed from the pure _I subunit.From our single channel data we conclude that ₁ accelerates the inactivation process of the sodium channel complex.     

Differential effects of malotilate on 5-, 12- and 15-lipoxygenase in human ascites cells

Conclusions These effects of malotilate on eicosanoid formation differ from those of known lipoxygenase inhibitors such as BW 755C (IC₅₀ of 5-lipoxygenase 35 M, 12-lipoxygenase >100 M and 15-lipoxygenase 1.2 M), nordihydroguiaretic acid (IC₅₀ of 5-lipoxygenase 1.4 M, 12-lipoxygenase 26 M and 15-lipoxygenase 1 M) and ketoconazole (5-lipoxygenase 28 M, 12-lipoxygenase not affected and 15-lipoxygenase increased) [5]. The differential effects of malotilate on the 5-, 12- and 15-lipoxygenases and also on the generation of the compounds of the cyclooxygenase, have not previously been reported. The suppression of leukotriene productionin vitro occurred at concentrations found following normal therapeutic dosesin vivo. Inhibition of the production of the chemotactic substance LTB₄ and the vasoconstrictive TxA₂ provide a possible explanation for the useful effects of this drug on liver necrosis and liver fibrosis.     

Specific patterns of neuron arrangement and of synaptic articulation in the medial geniculate body

Summary Golgi and electron microscopic analysis of the known cellular layers in concentric shells of the ventro-lateral portion of the medial geniculate body revealed a flat grid of high density neuropil filling the space between the geniculocortical relay cells, forming essentially a single cell layer in each lamina. The skeleton of this neuropil grid is made up by the interdigitating dendritic tufts of the geniculocortical relay cells, joined together by a rich system of desmosomoid adhesion plaques. The holes of the skeleton are filled in by the multilobed dendritic appendages of Golgi type II interneurons and the grape-like terminals of the inferior collicular specific afferents. Additional axon terminals of other sources — terminals of descending corticogenicular fibers, axons of the Golgi type II interneurons and terminals of the initial collaterals of the geniculocortical relay cells — contribute only to a very insignificant fraction of neuropil volume. The Golgi type II interneurons are oriented in perpendicular direction to the cell layers so that they may bridge with their dendrites several successive layers.Although the general expression synaptic glomeruli used in other relay nuclei for this type of specific synaptic arrangement is hardly applicable to this grid-like neuropil, the essential synaptic articulation pattern of all thalamic relay nuclei is well maintained. The specific inferior collicular afferents are presynaptic to both relay cell dendrites and to the multilobed dendritic appendages of Golgi type II cells, which in turn are presynaptic to the same dendritic regions of the relay cells receiving the bulk of the specific afferents.