000000709 001__ 709
000000709 005__ 20251230153425.0
000000709 0247_ $$2DOI$$a10.6083/M44747V3
000000709 037__ $$aETD
000000709 245__ $$aStudy of a glycine hinge in ATP-sensitive potassium channels
000000709 260__ $$bOregon Health and Science University
000000709 269__ $$a2012
000000709 336__ $$aDissertation
000000709 502__ $$bPh.D.
000000709 502__ $$gNeuroscience
000000709 520__ $$aPotassium channels regulate cell excitability by gating K⁺ flux through transmembrane pores. Inward rectifier (Kir) channels, including ATP-sensitive K⁺ (KATP) channels, rely on TM2 flexibility for gating, hypothesized to involve a glycine hinge. This study examined glycine mutations linked to congenital hyperinsulinism. Glycine-to-arginine substitution abolished conduction via electrostatic disruption, while a compensatory mutation restored function without affecting nucleotide regulation, indicating the hinge is not essential for gating. Glycine-to-proline mutation caused inactivation, likely due to impaired coupling between cytoplasmic and transmembrane domains. Findings refine the hinge hypothesis and advance understanding of Kir channel gating and disease mechanisms.
000000709 540__ $$fCC BY
000000709 542__ $$fIn copyright - single owner
000000709 650__ $$aIon Channels$$021013
000000709 650__ $$aIon Channel Gating$$028538
000000709 650__ $$aInsulin-Secreting Cells$$036369
000000709 650__ $$aPotassium Channels$$028230
000000709 650__ $$aMutation$$022555
000000709 6531_ $$aglycine hinge
000000709 6531_ $$apersistent hyperinsulinemia hypoglycemia of infancy
000000709 6531_ $$apancreatic beta cells
000000709 6531_ $$ainsulin shock
000000709 691__ $$aSchool of Medicine$$041369
000000709 692__ $$aVollum Institute$$041509
000000709 7001_ $$aBushman, Jeremy$$uOregon Health and Science University$$041354
000000709 7201_ $$aShow-Ling, Shyng$$uOregon Health and Science University$$041354$$7Personal$$eAdvisor
000000709 8564_ $$95a0a5187-f3da-4e88-b5cd-1d37389c1e4a$$s3159992$$uhttps://digitalcollections.ohsu.edu/record/709/files/711_etd.pdf$$ePublic$$206da09e50cb04a3c8126cb311d1e86a5$$31
000000709 905__ $$a/rest/prod/9z/90/2z/87/9z902z875
000000709 909CO $$ooai:digitalcollections.ohsu.edu:709$$pstudent-work
000000709 980__ $$aTheses and Dissertations