Accession Number:

ADA583974

Title:

M Current-Based Therapies for Nerve Agent Seizures

Descriptive Note:

Final rept. 1 Jul 2010-30 Jun 2013

Corporate Author:

VIRGINIA UNIV CHARLOTTESVILLE

Personal Author(s):

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

Report Date:

2013-07-01

Pagination or Media Count:

47.0

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 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.

Descriptors:

• *NERVE AGENTS
• *ORGANOPHOSPHATES
• AUGMENTATION
• CHOLINERGIC NERVES
• CONVULSIVE DISORDERS
• HIPPOCAMPUS
• MODULATION
• NERVE CELLS
• PARASYMPATHOLYTIC AGENTS
• POTASSIUM
• PYRAMIDS(GEOMETRY)
• TEST AND EVALUATION

Subject Categories:

• Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE