November 2010

Document Type


Degree Name



Oregon Health & Science University


The ATP-sensitive potassium channel (K[subsvript ATP]) is central to the translation of metabolic status into cellular electrical excitability. In no place is this more evident than pancreatic β-cells where K[subscript ATP] functions to translate blood glucose concentrations into insulin secretion. K[subscript ATP] dysfunction leads to a spectrum of life-threatening insulin secretion disorders usually presenting within the first days to weeks of life. Great strides have been made in understanding the molecular determinants of K[subscript ATP] function through the study of disease-causing mutations in the two proteins that make up its structure: the inward rectifier channel 6.2 (Kir6.2) and the sulfonylurea receptor1 (SUR1). Presented in this dissertation is the extensive analysis of two mutations in SUR1 (R74W and E128K) through mutagenesis screening that has led to numerous insights into K[subscript ATP] function. Both residues are vital to the maintenance of SUR1-Kir6.2 inter-connec




Neuroscience Graduate Program


School of Medicine



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