Altered Sodium Channels Underlie Anticonvulsant Drug Insensitivity
نویسندگان
چکیده
منابع مشابه
The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels.
We hypothesized that lacosamide modulates voltage-gated sodium channels (VGSCs) at clinical concentrations (32-100 muM). Lacosamide reduced spiking evoked in cultured rat cortical neurons by 30-s depolarizing ramps but not by 1-s ramps. Carbamazepine and phenytoin reduced spike-firing induced by both ramps. Lacosamide inhibited sustained repetitive firing during a 10-s burst but not within the ...
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The anticonvulsants phenytoin and carbamazepine interact allosterically with the batrachotoxin binding site of sodium channels. In the present study, we demonstrate an autoradiographic technique to localize the batrachotoxin binding site on sodium channels in rat brain using [3H]batrachotoxinin-A 20-alpha-benzoate (BTX-B). Binding of [3H]BTX-B to brain sections is dependent on potentiating allo...
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Immunocytochemical and electrophysiological techniques were used to localize TTX-sensitive sodium channels (NaChs) over the soma-dendritic axis of basilar and nonbasilar pyramidal cells of the electrosensory lateral line lobe (ELL) of weakly electric fish (Apteronotus leptorhynchus). Dense NaCh-like immunolabel was detected on the membranes of basilar and nonbasilar pyramidal cell somata. Punct...
متن کاملVoltage gated sodium channels as drug discovery targets.
Voltage-gated sodium (NaV) channels are a family of transmembrane ion channel proteins. They function by forming a gated, water-filled pore to help establish and control cell membrane potential via control of the flow of ions between the intracellular and the extracellular environments. Blockade of NaVs has been successfully accomplished in the clinic to enable control of pathological firing pa...
متن کاملMolecular model of anticonvulsant drug binding to the voltage-gated sodium channel inner pore.
The tricyclic anticonvulsant drugs phenytoin, carbamazepine, and lamotrigine block neuronal voltage-gated Na(+) channels, and their binding sites to domain IV-S6 in the channel's inner pore overlap with those of local anesthetic drugs. These anticonvulsants are neutral, in contrast to the mostly positively charged local anesthetics, but their open/inactivated-state blocking affinities are simil...
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ژورنال
عنوان ژورنال: Epilepsy Currents
سال: 2003
ISSN: 1535-7597,1535-7511
DOI: 10.1046/j.1535-7597.2003.03606.x