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Reduction of voltage-operated sodium currents by the anticonvulsant drug sulthiame
Authors:Michael Madeja  Christian Wolf  Erwin-Josef Speckmann
Institution:a Institut für Physiologie, Robert-Koch-Str. 27a, 48149 Münster, Germany;b Gemeinnützige Hertie-Stiftung, Bereich Neurowissenschaften/multiple Sklerose, Lyoner Straße 15, Im Atricom, D-60528, Frankfurt, Germany;c Desitin Arzneimittel GmbH, Weg beim Jäger 214, 22335 Hamburg, Germany
Abstract:The effect of the sulfonamide derivative sulthiame (Ospolot®) on voltage-operated sodium channels was investigated in acutely isolated neurons from the guinea pig hippocampus using the whole-cell patch-clamp technique. Sulthiame in a concentration of 10 μg/ml reduced the inactivating sodium currents without affecting potassium currents. The effect was not dependent on voltage. At therapeutic concentration of 1 to 10 μg/ml sodium currents were reduced by 13 to 25% of control. Reductions of this size (induced by the specific sodium channel blocker tetrodotoxin or by 10 μg/ml sulthiame itself) impaired repetitive generation of action potentials and reduced the maximum discharge frequency by 20 to 40%. In summary, the anticonvulsant drug sulthiame exerts blocking effects on sodium channels which can be assumed to be anticonvulsant and to be different from the effects induced by blockade of carbonic anhydrase.
Keywords:Isolated neuron  Sodium channel  Voltage-gated ion channel  Anticonvulsant drug  Carbonic anhydrase
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