The broad context of our research is the molecular basis, and functional role, of potassium channels. The early cloning of channel genes led to understanding the molecular basis of function by mutagenic and now crystallographic methods. In parallel, these basic studies have fueled the genetic manipulation of channels in recombinant organisms, in turn explaining ion channel diseases and informing clinical therapies. Our own major contributions include (1) the cloning and expression of novel K channel genes, (2) elucidation of the mechanism of K (Kir) channel rectification, (3) elucidation of the molecular basis of KATP channel function, (4) the first molecular model of the Kir channel pore, (5) transgenic animal models of diabetes, hyperinsulinism, and cardiac dysrrhythmias. Current major challenges range from atomic resolution of Kir channel structure and function, to further elucidation of the roles of Kir channels in organ function and dysfunction in the heart, pancreas, vasculature and brain.

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