Inward rectifying potassium (Kir) channels play key physiological roles in cardiac, neuronal, endocrine and epithelial cells and may represent novel therapeutic targets for several common disorders. However, the lack of selective pharmacological probes has thus far hampered efforts to assess their therapeutic potential. To overcome this barrier, we are using a combination of high-throughput screening, medicinal chemistry, conventional and fully automated patch clamp electrophysiology, mutagenesis and molecular modeling to develop potent and highly selective small-molecule probes for each family member (see Lewis et al., Mol Pharm, 2009). We are interested in working with highly motivated students and fellows who wish to combine these methods to develop a detailed understanding of Kir channel structure and pharmacology.

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Drug Discovery Electrophysiology Pharmacology Potassium Channels Structural Biology