POSTSYNAPTIC SIGNALING PATHWAYS

Project: Research project

Project Details

Description

DESCRIPTION: At the synapse, signals are transduced from one neuron to another: neurotransmitters are released upon depolarization from the presynaptic site and activate neurotransmitter receptors, i.e., ligand-gated ion channels, at the postsynaptic site. The long-term goal of the proposed studies is to determine signaling pathways at postsynaptic sites which modulate postsynaptic effector proteins. The research will focus on NMDA receptors, which are gated by glutamate, the prevailing excitatory neurotransmitter in mammalian brain, and on class C L-type channels, which have recently been shown to be specifically localized at postsynaptic sites of excitatory synapses. Overstimulation of Ca2+-permeable glutamate receptors has been implicated in neuropathologies caused by ischemia as occurs during strokes, by status epilepticus, and by brain traumata. There is some evidence that L-type Ca2+ channels play a role during Alzheimer's Disease which can be alleviated by chronic administration of the L-type channel blocker, nimodipine. Defining the modulation of these proteins may, therefore, help to understand and treat those neuropathologies. In detail, the signaling events controlling phosphorylation of these postsynaptic effector proteins by protein kinase A in acute hippocampal slices will be defined employing back-phosphorylation as well as immunochemical methods based on antibodies specific for the phosphorylated form of a defined phosphorylation site. NMDA-induced, calpain-mediated proteolytic processing of postsynaptic class C L-type channels in hippocampal slices emerges as a modification which activates these channels irreversibly. This phenomenon will be analyzed by drug treatment and subsequent immunochemical detection of processed class C L-type channels.
StatusFinished
Effective start/end date5/1/976/30/12

Funding

  • National Institutes of Health: $322,251.00
  • National Institutes of Health: $328,823.00
  • National Institutes of Health: $317,073.00
  • National Institutes of Health: $30,000.00
  • National Institutes of Health: $206,004.00
  • National Institutes of Health: $50,000.00
  • National Institutes of Health: $317,073.00
  • National Institutes of Health: $331,875.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $322,251.00
  • National Institutes of Health: $245,521.00
  • National Institutes of Health: $317,073.00
  • National Institutes of Health: $330,924.00
  • National Institutes of Health: $76,730.00
  • National Institutes of Health: $194,177.00

ASJC

  • Medicine(all)
  • Neuroscience(all)

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.