M Current-Based Therapies for Nerve Agent Seizures
Final rept. 1 Jul 2010-30 Jun 2013
VIRGINIA UNIV CHARLOTTESVILLE
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This is a proposal to develop novel, mechanism-based therapies for the treatment of organophosphate OP nerve agent-induced seizures. The primary goal of this proposal is to test two interrelated hypotheses 1 Cholinergic nerve agents cause neuronal hyper-excitability by inhibiting MKCNQ23 potassium channels. 2 Cholinergic seizures can be blocked by drugs that can open potassium channels mediating M currents. These hypotheses will be tested by accomplishing three aims. Aim 1 To test whether modulation of M channel modulators antagonists and openers glutamatergic transmission on CA1 pyramidal neurons and dentate granule cells. Aim 2 To characterize the effects of M current enhancers on excitabtility and bursting of CA1 pyramidal neurons. Aim 3 To test anticonvulsant action of three M-Channel openers in cholinergic overstimulation-induced status epilepticus.
- Chemical, Biological and Radiological Warfare