M Current-Based Therapies for Nerve Agent Seizures

Abstract

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 M/KCNQ2/3 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.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2013
Accession Number
ADA583974

Entities

People

  • Jaideep Kapur
  • Jian L. Sun
  • John Williamson
  • Marko Todorovic
  • Terry Zhang

Organizations

  • University of Virginia

Tags

DTIC Thesaurus Topics

  • Anticonvulsants
  • Brain
  • Cells
  • Chemistry
  • Epilepsy
  • Health Services
  • Membrane Potentials
  • Neurons
  • Poisoning
  • Rodents
  • Seizures

Fields of Study

  • Biology
  • Chemistry
  • Medicine

Readers

  • Neuroscience
  • Neurotoxicology