Sodium channel inactivation kinetics of rat sensory and motor nerve fibres and their modulation by glutathione

Na+ channel currents of rat motor and sensory nerve fibres were studied with the patch-clamp technique on enzymatically demyelinated axons. Differences between motor and sensory fibres in multi-channel inactivation kinetics and the gating of late single-channel currents were investigated. In the axon-attached mode, inactivation of multi-channel Na+ currents in sensory axons was best fitted with a single time constant while for motor axons two time constants were needed. Late single-channel currents in sensory axons were characterized by short openings whereas motor axons exhibited additional long single-channel openings. In contrast, in excised, inside-out membrane patches, no differences between motor and sensory fibres were found: in both types of fibre inactivation of multi-channel Na+ currents proceeded with two time constants and late single-channel currents showed short and long openings. After application of the reducing agent glutathione to the cytoplasmic side of excised inside-out patches, inactivation of Na+ currents in both motor and sensory fibres proceeded with a single, fast exponential time constant and late currents appeared with short openings only. These data indicate that the axonal metabolism may contribute to the different inactivation kinetics of Na+ currents in motor and sensory nerve fibres

Sodium channel inactivation kinetics of rat sensory and motor nerve fibres and their modulation by glutathione

Na+ channel currents of rat motor and sensory nerve fibres were studied with the patch-clamp technique on enzymatically demyelinated axons. Differences between motor and sensory fibres in multi-channel inactivation kinetics and the gating of late single-channel currents were investigated. In the axon-attached mode, inactivation of multi-channel Na+ currents in sensory axons was best fitted with a single time constant while for motor axons two time constants were needed. Late single-channel currents in sensory axons were characterized by short openings whereas motor axons exhibited additional long single-channel openings. In contrast, in excised, inside-out membrane patches, no differences between motor and sensory fibres were found: in both types of fibre inactivation of multi-channel Na+ currents proceeded with two time constants and late single-channel currents showed short and long openings. After application of the reducing agent glutathione to the cytoplasmic side of excised inside-out patches, inactivation of Na+ currents in both motor and sensory fibres proceeded with a single, fast exponential time constant and late currents appeared with short openings only. These data indicate that the axonal metabolism may contribute to the different inactivation kinetics of Na+ currents in motor and sensory nerve fibres

High conductance anion channel in Schwann cell vesicles from rat spinal roots

Potassium uptake, possibly together with chloride, is one of the presumed functions of Schwann cells in the peripheral nervous system. However, the presence of chloride channels has not been demonstrated in adult Schwann cells. We present here a new method which allows single channel recordings to be made from Schwann cells in situ without enzymatic treatment. Isolated rat spinal roots were split mechanically into several bundles. Within about 30 min after this procedure small belb-like vesicles (20-30 m in diameter) with a clean surface appeared at the edges of the fibre bundles. Immunofluorescence microscopy with a surface marker for Schwann cell membranes (monoclonal antibody O4) revealed that the vesicles originate from Schwann cells. In standard patch clamp recordings with symmetrical bath and pipette solutions (excised inside-out configuration) an anion channel with the following characteristics was mainly observed: (1) single channel slope conductance of 337 ± 5 pS in 125 mM KCl and 209 ± 6 pS in 125 mM K+ methylsulphate; (2) ion permeability ratio: PCl/PK/Pgluconate = 1/0.12/0.06; (3) linear current-voltage relationship (range ± 60 mV) and (4) voltage- and time-dependent inactivation (the channel was most active at potentials ± 20mV). Pharmacologically, the channel was completely blocked with zinc (1 mM) and barium (10 mM). A similar anion channel, showing characteristics 1 - (4), has been described in cultured Schwann cells of newborn rats (Gray et al., 1984). We now demonstrate that this channel is also present in adult Schwann cells in situ

Four and a half LIM protein 1C (FHL1C)

Four-and-a-half LIM domain protein 1 isoform A (FHL1A) is predominantly expressed in skeletal and cardiac muscle. Mutations in the FHL1 gene are causative for several types of hereditary myopathies including X-linked myopathy with postural muscle atrophy (XMPMA). We here studied myoblasts from XMPMA patients. We found that functional FHL1A protein is completely absent in patient myoblasts. In parallel, expression of FHL1C is either unaffected or increased. Furthermore, a decreased proliferation rate of XMPMA myoblasts compared to controls was observed but an increased number of XMPMA myoblasts was found in the G(0)/G(1) phase. Furthermore, low expression of K(v1.5), a voltage-gated potassium channel known to alter myoblast proliferation during the G(1) phase and to control repolarization of action potential, was detected. In order to substantiate a possible relation between K(v1.5) and FHL1C, a pull-down assay was performed. A physical and direct interaction of both proteins was observed in vitro. In addition, confocal microscopy revealed substantial colocalization of FHL1C and K(v1.5) within atrial cells, supporting a possible interaction between both proteins in vivo. Two-electrode voltage clamp experiments demonstrated that coexpression of K(v1.5) with FHL1C in Xenopus laevis oocytes markedly reduced K(+) currents when compared to oocytes expressing K(v1.5) only. We here present the first evidence on a biological relevance of FHL1C

Four and a Half LIM Protein 1C (FHL1C): A Binding Partner for Voltage-Gated Potassium Channel Kv1.5

Four-and-a-half LIM domain protein 1 isoform A (FHL1A) is predominantly expressed in skeletal and cardiac muscle. Mutations in the FHL1 gene are causative for several types of hereditary myopathies including X-linked myopathy with postural muscle atrophy (XMPMA). We here studied myoblasts from XMPMA patients. We found that functional FHL1A protein is completely absent in patient myoblasts. In parallel, expression of FHL1C is either unaffected or increased. Furthermore, a decreased proliferation rate of XMPMA myoblasts compared to controls was observed but an increased number of XMPMA myoblasts was found in the G0/G1 phase. Furthermore, low expression of Kv1.5, a voltage-gated potassium channel known to alter myoblast proliferation during the G1 phase and to control repolarization of action potential, was detected. In order to substantiate a possible relation between Kv1.5 and FHL1C, a pull-down assay was performed. A physical and direct interaction of both proteins was observed in vitro. In addition, confocal microscopy revealed substantial colocalization of FHL1C and Kv1.5 within atrial cells, supporting a possible interaction between both proteins in vivo. Two-electrode voltage clamp experiments demonstrated that coexpression of Kv1.5 with FHL1C in Xenopus laevis oocytes markedly reduced K+ currents when compared to oocytes expressing Kv1.5 only. We here present the first evidence on a biological relevance of FHL1C

Web Services for Language Resources and Language Technology Applications

In this paper we discuss the application of web service technology to the language technology (LT) and corpus processing domain. Motivated by a host of language technology tools which are widely available but which lack common technical standards for integrat-ing them into language technology applications we discuss the implementation of a web service-based API for web-based processing and accessing of large linguistic data resources

Automatic acquisition of paradigmatic relations using iterated co-occurrences

We introduce the notion of iterated co-occurrences, which can be obtained by performing the calculation of statistically significant cooccurrences not on sentence level, but on co-occurrence sets of previous calculations. The underlying mechanisms are explained in detail and we give reasons, why this iteration results in sets of semantically homogeneous words. These can be used for the automatic acquisition of paradigmatic relations in order to semi-automatically extend lexical-semantic word nets or thesauri, widening the acquisition bottleneck. A small evaluation for synset expansion for German language and some discussion conclude the work. 1

Energy efficient non-road hybrid electric vehicles: advanced modeling and control

Analyzing the main problems in the real-time control of parallel hybrid electric powertrains in non-road applications, which work in continuous high dynamic operation, this book gives practical insight in to how to maximize the energetic efficiency and drivability of such powertrains. The book addresses an energy management control structure, which considers all constraints of the physical powertrain and uses novel methodologies for the prediction of the future load requirements to optimize the controller output in terms of an entire work cycle of a non-road vehicle. The load prediction includes a methodology for short term loads as well as for an entire load cycle by means of a cycle detection. A maximization of the energetic efficiency can so be achieved, which is simultaneously a reduction in fuel consumption and exhaust emissions. Readers will gain a deep insight into the necessary topics to be considered in designing an energy and battery management system for non-road vehicles and that only a combination of the management systems can significantly increase the performance of a controller

Small worlds of concepts and other principles of semantic search

A combination of the strengths of both classic information retrieval with the distributed approach of P2P networks can avoid both their weaknesses: The organisation of document collections relevant for special communities allows both high coverage and quick access. We present a theoretical framework in which the semantic structure between words can be deduced from a document collection. This structural knowledge can then be used to connect document collections to communities based on their content