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  • 1
    Electronic Resource
    Electronic Resource
    On identification of Na+ channel gating schemes using moving-average filtered hidden Markov models (1999)
    Springer
    European biophysics journal 28 (1999), S. 605-609 
    Details
    ISSN: 1432-1017
    Keywords: Key words Single channel recording ; Sodium channel ; Gating scheme ; Hidden Markov model ; Anti-aliasing filter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract  Transitions between distinct kinetic states of an ion channel are described by a Markov process. Hidden Markov models (HMM) have been successfully applied in the analysis of single ion channel recordings with a small signal-to-noise ratio. However, we have recently shown that the anti-aliasing low-pass filter misleads parameter estimation. Here, we show for the case of a Na+ channel recording that the standard HMM do neither allow parameter estimation nor a correct identification of the gating scheme. In particular, the number of closed and open states is determined incorrectly, whereas a modified HMM considering the anti-aliasing filter (moving-average filtered HMM) is able to reproduce the characteristic properties of the time series and to perform gating scheme identification.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002490050243
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  • 2
    Electronic Resource
    Electronic Resource
    Enhanced inactivation and acceleration of activation of the sodium channel associated with epilepsy in man (2001)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 13 (2001), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Generalized epilepsy with febrile seizures-plus (GEFS+) is a benign Mendelian syndrome characterized by childhood-onset febrile and afebrile seizures. Three point mutations within two voltage-gated sodium channel genes have been identified so far: in GEFS+ type 1 a mutation in the β1-subunit gene SCN1B, and in GEFS+ type 2 two mutations within the neuronal α-subunit gene SCN1A. Functional expression of the SCN1B and one of the SCN1A mutations revealed defects in fast channel inactivation which are in line with previous findings on myotonia causing mutations in SCN4A, the skeletal muscle sodium channel α-subunit gene, all showing an impaired fast inactivation. We now studied the second GEFS+ mutation (T875M in SCN1A), using the highly homologous SCN4A gene (mutation T685M). Unexpectedly, the experiments revealed a pronounced enhancement of both fast and slow inactivation and a defect of channel activation for T685M compared to wild-type channels. Steady-state fast and slow inactivation curves were shifted in the hyperpolarizing direction, entry into slow inactivation was threefold accelerated, recovery from slow inactivation was slowed by threefold and the time course of activation was slightly but significantly accelerated. In contrast to other disease-causing mutations in SCN1A, SCN1B and SCN4A, the only mechanism that could explain hyperexcitability of the cell membrane would be the acceleration of activation. Because the enhancement of slow inactivation was the most obvious alteration in gating found for T685M, this might be the disease-causing mechanism for that mutation. In this case, the occurrence of epileptic seizures could be explained by a decrease of excitability of inhibitory neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0953-816x.2001.01590.x
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  • 3
    Electronic Resource
    Electronic Resource
    Molecular analysis of the A322D mutation in the GABAA receptor α1-subunit causing juvenile myoclonic epilepsy (2005)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 22 (2005), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Juvenile myoclonic epilepsy (JME) belongs to the most common forms of hereditary epilepsy, the idiopathic generalized epilepsies. Although the mode of inheritance is usually complex, mutations in single genes have been shown to cause the disease in some families with autosomal dominant inheritance. The first mutation in a multigeneration JME family has been recently found in the α1-subunit of the GABAA receptor (GABRA1), predicting the single amino acid substitution A322D. We further characterized the functional consequences of this mutation by coexpressing α1-, β2- and γ2-subunits in human embryonic kidney (HEK293) cells. By using an ultrafast application system, mutant receptors have shown reduced macroscopic current amplitudes at saturating GABA concentrations and a highly reduced affinity to GABA compared to the wild-type (WT). Dose–response curves for current amplitudes, activation kinetics, and GABA-dependent desensitization parameters showed a parallel shift towards 30- to 40-fold higher GABA concentrations. Both deactivation and resensitization kinetics were considerably accelerated in mutant channels. In addition, mutant receptors labelled with enhanced green fluorescent protein (EGFP) were not integrated in the cell membrane, in contrast to WT receptors. Therefore, the A322D mutation leads to a severe loss-of-function of the human GABAA receptor by several mechanisms, including reduced surface expression, reduced GABA-sensitivity, and accelerated deactivation. These molecular defects could decrease and shorten the resulting inhibitory postsynaptic currents (IPSCs) in vivo, which can induce a hyperexcitability of the postsynaptic membrane and explain the occurrence of epileptic seizures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.2005.04168.x
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  • 4
    Electronic Resource
    Electronic Resource
    Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies (2003)
    [s.l.] : Nature Publishing Group
    Nature genetics 33 (2003), S. 527-532 
    Details
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Idiopathic generalized epilepsy (IGE) is an inherited neurological disorder affecting about 0.4% of the world's population. Mutations in ten genes causing distinct forms of idiopathic epilepsy have been identified so far, but the genetic basis of many IGE subtypes is still unknown. Here we report a ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/ng1121
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  • 5
    Electronic Resource
    Electronic Resource
    Teaching course: ion channelopathies in neurology (1999)
    Springer
    Journal of neurology 246 (1999), S. 758-763 
    Details
    ISSN: 1432-1459
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050451
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  • 6
    Electronic Resource
    Electronic Resource
    Anlagerung von Basen an 3-Nitro-N-methyl-chinoliniumjodid (1968)
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 101 (1968), S. 2731-2737 
    Details
    ISSN: 0009-2940
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Bei der Reduktion von 3-Nitro-N-methyl-chinoliniumjodid (1a) mit Natriumborhydrid erhält man nebeneinander die 1.2-Dihydroverbindung 4a und die 1.4-Dihydroverbindung 5a. 4a läßt sich in 5a umlagern. Der Mechanismus dieser Wasserstoffverschiebung ist noch nicht geklärt. Anionen CH-acider Verbindungen, Hydroxyl- und Alkoholat-Ionen sowie Amine werden von 1a in 4-Stellung addiert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cber.19681010815
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  • 7
    Electronic Resource
    Electronic Resource
    Umsetzungen heterocyclischer Nitroverbindungen, II. Anlagerung von Basen an 3-Nitro-N-methyl-pyridiniumjodid (1969)
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 102 (1969), S. 2163-2168 
    Details
    ISSN: 0009-2940
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 3-Nitro-N-methyl-pyridiniumjodid (1) lagert Anionen CH-acider Verbindungen sowie Piperidin in 4-Stellung an (→ 2 bzw. 6). Durch Natriumborhydrid wird 1 überwiegend zur 1.4-Dihydroverbindung (7), 3-Nitro-1.4-dimethyl-pyridiniumjodid (9) dagegen zur 1.2-Dihydroverbindung (10) reduziert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cber.19691020702
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  • 8
    Electronic Resource
    Electronic Resource
    Versuche zur Darstellung von Endiazeniumsalzen (1985)
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 118 (1985), S. 3011-3019 
    Details
    ISSN: 0009-2940
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Experiments to Form Enediazenium Salts(2-Alkoxyvinyl)diazenium salts 9 and 14 are obtained by O-alkylation of glyoxal- (4) and methylglyoxal monodimethylhydrazone (13), resp., with alkyl trifluoromethanesulfonates. Bromination of N-(trimethylsilyl)enehydrazines 16 and 18 in pentane leads to the formation of solid, hydrophilic substances, for which the structures of enediazenium salts 19, α-bromohydrazones 20, or ammonium salts 21 are discussed. These compounds react with nucleophiles (alcohols, amines, thiols, and indole) to give hydrazones 24a-i substituted at C-2.
    Notes: Glyoxal- (4) und Methylglyoxal-monodimethylhydrazon (13) werden durch Trifluormethansulfonsäure-alkylester am Sauerstoff zu (Alkoxyvinyl)diazeniumsalzen 9 bzw. 14 alkyliert. N-Silylierte Enhydrazine 16 und 18ergeben mit Brom in Pentan feste, hydrophile Verbindungen, für die die Strukturen von Endiazeniumsalzen 19 oder α-Bromhydrazonen 20 bzw. Ammoniumsalzen 21 diskutiert werden. Diese Verbindungen addieren Alkohole, Amine, Thiole sowie Indol als Nucleophile am C-Atom 2 unter Bildung der Hydrazone 24a-i.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cber.19851180802
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  • 9
    Electronic Resource
    Electronic Resource
    Umsetzungen von Dimethylhydrazonen ungesättigter Aldehyde mit elektrophilen Reagenzien (1984)
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 117 (1984), S. 2875-2885 
    Details
    ISSN: 0009-2940
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Reactions of Unsaturated Aldehyde Dimethylhydrazones with Electrophilic ReagentsCrotonaldehyde dimethylhydrazone (1) is substituted at C-3 by electrophiles such as chlorine, bromine, iodine, arylsulfenyl chloride, phenylsulfinyl chloride, and nitronium tetrafluoroborate to form the products 10a  -  c, 18a, b, 25, and 26. In contrast, from 1 and p-nitrobenzoyl chloride the dienehydrazide 3 is obtained. Acrolein dimethylhydrazone reacts with diazoacetic ester to give the cyclopropane derivative 29. Isoxazole 32 is obtained from 28 and p-chlorobenzonitrile oxide.
    Notes: Crotonaldehyd-dimethylhydrazon (1) wird durch elektrophile Reagenzien wie Chlor, Brom, Iod, N-Chlorsuccinimid, Arylsulfenylchlorid, Phenylsulfinylchlorid oder Nitryl-tetrafluoroborat and C-3 unter Bildung der Produkte 10a  -  c, 18a, b, 25 und 26 substituiert. Bei Einwirkung von p-Nitrobenzoylchlorid auf 1 erhält man dagegen das Dienhydrazid 3. Acrolein-dimethylhydrazon (28) reagiert mit Diazoessigester zum Cyclopropanderivat 29, mit p-Chlorbenzonitriloxid zum Isoxazolin 32.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cber.19841170909
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  • 10
    Electronic Resource
    Electronic Resource
    Umsetzungen mit Nitroenaminen, XII. Umsetzung von Estern und Lactonen mit Nitroenaminen (1974)
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 107 (1974), S. 1509-1517 
    Details
    ISSN: 0009-2940
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Reactions with Nitroenamines, XII. Reaction of Esters and Lactones with NitroenaminesLithium salts of carboxylic esters and lactones with a methylene group in the α-position react with 1-dimethylamino-2-nitroethylene or 1-dimethylamino-2-nitro-1-propene to give the corresponding aci-nitroethylidene- or aci-nitropropylidene derivatives (3 + 4 → 5). On silica gel the compounds 5d - k are transformed into the keto esters 9d - k.
    Notes: Ester von Carbonsäuren sowie Lactone mit α-ständiger Methylen-Gruppe lassen sich über die Lithium-Salze mit 1-Dimethylamino-2-nitroäthylen oder 1-Dimethylamino-2-nitro-1-propen zu aci-Nitroäthyliden- bzw. aci-Nitropropyliden-Derivaten umsetzen (3 + 4 → 5). Die Verbindungen 5d - k gehen auf Kieselgel in die Ketoester 9d - k über.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cber.19741070511
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