Show simple item record

dc.contributor.authorAgwa, Dalia
dc.date.accessioned2016-04-05T19:59:52Z
dc.date.available2016-04-05T19:59:52Z
dc.date.issued2015
dc.identifier.isbn9781321568936
dc.identifier.other1658213526
dc.identifier.urihttp://hdl.handle.net/10477/51676
dc.description.abstractInflammatory pain is a neural response mechanism to tissue damage that is characterized by dorsal root ganglia (DRG) neuronal hyperexcitability. The involvement of Protein kinase A (PKA) in this process is well-established and is believed to directly cause neuronal hyperexcitability and the symptoms of hyperalgesia observed during inflammatory pain. Activation of the PKA pathway by inflammatory mediators such as prostaglandin E2 (PGE2) leads to changes in ion channel properties in the DRG neurons. Our group previously showed that PKA modulates the membrane expression of Slack channels, a subtype of sodium-activated potassium channels (KNa) that control firing accommodation in DRG neurons. The Slack channel contains a "post synaptic density, drosophila disc large tumor suppressor, zonula occludens-1" (PDZ) binding domain at the end of its C-terminus. PDZ domains are protein-protein interaction segments that act as scaffolds for clustering different signaling complexes that can modulate channel activity. I sought to probe the interactions at the PDZ domain of DRG Slack channels with a peptide consisting of the highly conserved last 10 amino acids of the Slack C-terminus. I showed that the application of the peptide alone to the embryonic DRG neuronal cultures can lead to neuronal hyperexcitability 50% of the time. The peptide acted in a similar manner to PKA phosphorylation and caused Slack channel internalization from the neuronal membrane as determined by membrane biotinylation assays. A scrambled version of the peptide produced no effect. These results suggest that the binding of the Slack channels to a PDZ scaffold is critical in keeping them at the membrane and may prevent the internalization of Slack channels. Identifying and understanding the entities involved in the trafficking of Slack channels and disrupting their activity during inflammation could lead to the development of novel analgesics to treat pain.
dc.languageEnglish
dc.sourceDissertations & Theses @ SUNY Buffalo,ProQuest Dissertations & Theses Global
dc.subjectBiological sciences
dc.subjectChannel internalization
dc.subjectChannel trafficking
dc.subjectIdentifying mechanisms
dc.subjectMyristoylated peptides
dc.subjectPotassium channels
dc.subjectSlack channels
dc.titleIdentifying mechanisms that control slack channel trafficking
dc.typeDissertation/Thesis


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record