000000853 001__ 853
000000853 005__ 20260120144839.0
000000853 0247_ $$2DOI$$a10.6083/M4CZ355B
000000853 037__ $$aETD
000000853 245__ $$aSelf repair in a zebrafish model for slow-channel myasthenic syndrome
000000853 260__ $$bOregon Health and Science University
000000853 269__ $$a2012
000000853 336__ $$aThesis
000000853 502__ $$bPh.D.
000000853 520__ $$aSlow channel syndrome (SCS) is a congenital myasthenic disorder caused by mutations in nicotinic acetylcholine receptor (AChR) subunits, prolonging channel openings and impairing neuromuscular transmission. Using the zebrafish twister mutant, which mimics human SCS but undergoes natural recovery, we identified two abnormal kinetic components linked to embryonic and adult AChR isoforms. Recovery occurs via developmental replacement of embryonic subunits, restoring synaptic function. Blocking embryonic subunit translation accelerated recovery, and quinidine, an open-channel blocker, improved motility by normalizing synaptic current decay. These findings reveal mechanisms of SCS pathogenesis and suggest therapeutic strategies for myasthenic syndromes.
000000853 540__ $$fCC BY
000000853 542__ $$fIn copyright - single owner
000000853 650__ $$aZebrafish$$028076
000000853 650__ $$aSynapses$$026704
000000853 650__ $$aMyasthenic Syndromes, Congenital$$032298
000000853 650__ $$aNeuromuscular Junction$$022853
000000853 650__ $$aAcetylcholine$$014113
000000853 650__ $$aPhysiology$$024123
000000853 650__ $$aPterygium$$024876
000000853 650__ $$aReceptors, Nicotinic$$025212
000000853 650__ $$aReceptors, Cholinergic$$025186
000000853 691__ $$aSchool of Medicine$$041369
000000853 7001_ $$aWalogorsky, Michael$$uOregon Health and Science University$$041354
000000853 7201_ $$aBrehm, Paul$$uOregon Health and Science University$$041354$$7Personal$$eAdvisor
000000853 8564_ $$98fcecfc6-f82e-4b9c-82d1-7500a160075a$$s4708714$$uhttps://digitalcollections.ohsu.edu/record/853/files/856_etd.pdf$$ePublic$$21747d9fdfbb4ca7d48f8380934a1e361$$31
000000853 905__ $$a/rest/prod/bg/25/7f/08/bg257f089
000000853 909CO $$ooai:digitalcollections.ohsu.edu:853$$pstudent-work
000000853 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument
000000853 980__ $$aTheses and Dissertations