Voltage-gated ion channels

Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Current Biology (Impact Factor: 9.57). 02/2005; 15(2):R44-7. DOI: 10.1016/j.cub.2004.12.050
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Available from: Zara A Sands, Jun 05, 2014
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    • "Several mechanisms have been proposed to explain how the sensor movement changes the channel conformation but this phenomenon remains unclear [4]. Voltage-regulated potassium ion permeability is critical in cellular excitability. "
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    ABSTRACT: Voltage-gated K(+) ion channels (VKCs) are membrane proteins that regulate the passage of potassium ions through membranes. This work reports a classification scheme of VKCs according to the signs of three electrophysiological variables: activation threshold voltage (V(t)), half-activation voltage (V(a50)) and half-inactivation voltage (V(h50)). A novel 3D pseudo-folding graph representation of protein sequences encoded the VKC sequences. Amino acid pseudo-folding 3D distances count (AAp3DC) descriptors, calculated from the Euclidean distances matrices (EDMs) were tested for building the classifiers. Genetic algorithm (GA)-optimized support vector machines (SVMs) with a radial basis function (RBF) kernel well discriminated between VKCs having negative and positive/zero V(t), V(a50) and V(h50) values with overall accuracies about 80, 90 and 86%, respectively, in crossvalidation test. We found contributions of the "pseudo-core" and "pseudo-surface" of the 3D pseudo-folded proteins to the discrimination between VKCs according to the three electrophysiological variables.
    Journal of Molecular Graphics and Modelling 07/2008; 26(8):1306-14. DOI:10.1016/j.jmgm.2008.01.001 · 1.72 Impact Factor
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    • "It is composed of six transmembrane helical segments and each monomer consists of a pore domain and a voltage sensor. At present the scientific community is divided concerning views on the conformation and orientation of the voltage sensor upon membrane depolarisation [104]. Nevertheless, there is the consensus that the voltage sensor of Kv channels forms an independent domain. "
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    ABSTRACT: Despite the complexity of ion-channels, MD simulations based on realistic all-atom models have become a powerful technique for providing accurate descriptions of the structure and dynamics of these systems, complementing and reinforcing experimental work. Successful multidisciplinary collaborations, progress in the experimental determination of three-dimensional structures of membrane proteins together with new algorithms for molecular simulations and the increasing speed and availability of supercomputers, have made possible a considerable progress in this area of biophysics. This review aims at highlighting some of the work in the area of potassium channels and molecular dynamics simulations where numerous fundamental questions about the structure, function, folding and dynamics of these systems remain as yet unresolved challenges.
    Central European Journal of Chemistry 09/2007; 5(3):635-671. DOI:10.2478/s11532-007-0028-6 · 1.33 Impact Factor
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    ABSTRACT: A novel, voltage-gated sodium channel cDNA, designated NaCh6, has been isolated from the rat central and peripheral nervous systems. RNase protection assays showed that NaCh6 is highly expressed in the brain, and NaCh6 mRNA is as abundant or more abundant than the mRNAs for previously identified rat brain sodium channels. In situ hybridization demonstrated that a wide variety of neurons express NaCh6, including motor neurons in the brainstem and spinal cord, cerebellar granule cells, and pyramidal and granule cells of the hippocampus. RT-PCR and/or in situ hybridization showed that astrocytes and Schwann cells express NaCh6. Thus, this sodium channel is broadly distributed throughout the nervous system and is shown to be expressed in both neurons and glial cells.
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