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  • 1
    Electronic Resource
    Electronic Resource
    Inactivation determined by a single site in K+ pores (1993)
    Springer
    Pflügers Archiv 422 (1993), S. 354-363 
    Details
    ISSN: 1432-2013
    Keywords: K+ channel inactivation ; N-type inactivation ; C-type inactivation ; Pore or P-type inactivation ; External TEA enhancement of current ; External K+ enhancement of current ; Conductance ; Pore mutations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An N-terminus peptide or a C-terminus mechanism involving a single residue in transmembrane segment 6 produces inactivation in voltage-dependent K+ channels. Here we show that a single position in the pore of K+ channels can produce inactivation having characteristics distinct from either N- or C-type inactivation. In a chimeric K+ channel (CHM), the point reversion CHM V 369I produced fast inactivation and CHM V 369S had the additional effect of halving K+ conductance consistent with a position in the pore. The result was not restricted to CHM; mutating position 369 in the naturally occurring channel Kv2.1 also produced fast inactivation. Like N- and C-types of inactivation, pore or P-type inactivation was characterized by short bursts terminated by rapid entry into the inactivated state. Unlike C-type inactivation, in which external tetraethylammonium (TEA) produced a simple blockade that slowed inactivation and reduced currents, in P-type inactivation external TEA increased currents. Unlike N-type inactivation, internal TEA produced a simple reduction in current and K+ occupancy of the pore had no effect. External TEA was not the only cation to increase current; external K+ enhanced channel availability and recovery from inactivation. Additional features of P-type inactivation were residue-specific effects on the extent of inactivation and removal of inactivation by a point reversion at position 374, which also regulates conductance. The demonstration of P-type inactivation indicates that pore residues in K+ channels may be part of the inactivation gating machinery.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00374291
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  • 2
    Electronic Resource
    Electronic Resource
    Experimentelle Daten zu den Interaktionen von a2-Adrenozeptoragonisten mit Anästhetika, Analgetika, Lokalanästhetika (1996)
    Springer
    Der Schmerz 10 (1996), S. 14-20 
    Details
    ISSN: 1432-2129
    Keywords: Schlüsselwörterα2-Adrenozeptor-Agonisten: Clonidin ; Opioide: Morphin ; Lokalanästhetika: Bupivacain ; Anästhesietechnik: regional ; rückenmarksnah ; Pharmakologie: Interaktionen: additiv ; synergistisch ; Nozizeption ; Key wordsα2-Adrenoceptor agonists ; Opioids ; Local anaesthetics ; Regional anaesthesia ; Neuraxial anaesthesia ; Interactions ; Additive effect ; Synergistic effect ; Nociception
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The interactions of α2-adrenoceptor agonists with anaesthetics, analgesics and local anaesthetics are not only of practical importance in many areas of anaesthesia and pain therapy, but also of significant theoretical interest. Laboratory investigations and animal research allow us to study the pharmacological mechanisms of these drug interactions by using the tools of molecular biology. This may lead to the establishment of a scientific basis allowing the definition of rational drug therapies. In the first part of this overview, recent data on local anaesthetic effects of α2-adrenoceptor agonists on peripheral nerve conduction and their interaction with local anaesthetics are presented. Some important experimental work focusing on additive and synergistic spinal interactions of α2-adrenoceptor agonists with opioids and some other agents are then discussed. Finally, there is a brief reference to the central role of the spinal cord in mediating and controlling nociception.
    Notes: Zusammenfassung Die Interaktionen der α2-Adrenozeptoragonisten mit Anästhetika, Analgetika und Lokalanästhetika sind nicht nur von praktischer Bedeutung für viele Bereiche der Anästhesie und Schmerztherapie, sondern auch von theoretischem Interesse, weil gerade im Laborexperiment und im Tierversuch wichtige molekularbiologische Mechanismen und physiologische Grundlagen der pharmakologischen Interaktionen untersucht und dargestellt werden können. In dieser Übersichtsarbeit werden Untersuchungen zu den lokalanästhetischen Effekten der α2-Adrenozeptoragonisten am peripheren Nerven und ihre Interaktionen mit Lokalanästhetika vorgestellt. Dann werden einige laborexperimentelle Arbeiten zusammengefaßt, in denen additive und supraadditive spinale Interaktionen von α2-Adrenozeptoragonisten mit Opioiden, Physostgimin, Carbachol, Adenosin, Midazolam und Ketorolac nachgewiesen werden konnten. Schließlich soll die zentrale Rolle des Rückenmarks im Rahmen der physiologischen Kontrolle der Nozizeption kurz diskutiert werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004820050015
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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