Inward rectifier potassium (Kir) channels are a family of two transmembrane-spanning potassium selective ion channels. Kir channels are found in all kingdoms of life where they play essential roles in regulating numerous physiological functions. Mutations affecting Kir channels result in various diseases ranging from cardiac, neurological, renal and metabolic defects. Therefore, Kir channels represent important therapeutic targets. However, the Kir channel small-molecule pharmacology remains limited, which has impeded progress toward understanding their integral physiology and druggability. Since the emergence of insecticide-resistance in mosquito populations against current vector control agents, such as pyrethroids, efforts to decrease the transmission of vector-borne diseases are becoming less efficacious. As a result, we are facing a critical need for novel control agents. In mosquitoes, Kir channel functions remain largely unknown and their insecticidal potential unexplored. In an effort to expand the small-molecule pharmacology of Kir channels, we employed a broad array of experimental techniques, including molecular biology, fluorescence-based high-throughput screening, conventional and automated patch clamp electrophysiology, in conjunction with medicinal chemistry and mosquito bioassays to discover, optimize and characterize new modulators of Kir channel functions for the development of new therapeutics and insecticides.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-05182014-141528 |
| Date | 28 May 2014 |
| Creators | Raphemot, Rene |
| Contributors | Jerod S. Denton, Julián F. Hillyer, Corey R. Hopkins, C. David Weaver, Charles C. Hong |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-05182014-141528/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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