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    Sodium currents in striatal neurons from dystonic dt(sz) hamsters:
    altered response to lamotrigine (2002)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Siep, E
    Richter, A
    Löscher, W
    Speckmann, E-J
    Köhling, R
    Quelle
    Neurobiology of Disease; 9(2) — S. 258–268
    ISSN: 0969-9961
    Sprache
    Englisch
    Verweise
    Pubmed: 11895377
    Kontakt
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
    Tel.+49 30 838 53221 Fax.+49 30 838 53112
    email:pharmakologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Dystonic mutant dt(sz) hamsters are a model for paroxysmal dystonia. Handling/stress provoke the dystonic attacks. This phenomenon subsedes with maturation, but can be reinvoked when these animals receive sodium channel blockers such as lamotrigine, suggesting a dysfunction of striatal sodium channels. Voltage-gated fast sodium currents (I(Na(+))) were studied in acutely isolated striatal neurons from healthy and dt(sz) hamsters in whole-cell voltage clamp recordings. The action of lamotrigine was tested on (a) current/voltage relationship, (b) kinetics, and (c) steady-state inactivation and activation. Under control conditions, properties of I(Na(+)) were not different between healthy and dt(sz) neurons. With lamotrigine, however, (a) peak currents were significantly less depressed by the drug in neurons from dt(sz) hamsters as compared to healthy cells, and (b) the steady-state inactivation curve shift of I(Na(+)) was less pronounced in dt(sz) neurons. The results suggest that in dt(sz) hamsters, fast sodium currents in striatal neurons are more resistant to blockade. This sodium channel alteration might be causal for a functional imbalance between input and output structures of the basal ganglia under conditions of compromised I(+)(Na).