TY  - THES
AB  - Slow 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.
AD  - Oregon Health and Science University
AU  - Walogorsky, Michael
DA  - 2012
DO  - 10.6083/M4CZ355B
DO  - DOI
ED  - Brehm, Paul
ED  - Advisor
ID  - 853
KW  - Zebrafish
KW  - Synapses
KW  - Myasthenic Syndromes, Congenital
KW  - Neuromuscular Junction
KW  - Acetylcholine
KW  - Physiology
KW  - Pterygium
KW  - Receptors, Nicotinic
KW  - Neuromuscular Junction
KW  - Receptors, Cholinergic
KW  - Myasthenic Syndromes, Congenital
KW  - Zebrafish
L1  - https://digitalcollections.ohsu.edu/record/853/files/856_etd.pdf
L2  - https://digitalcollections.ohsu.edu/record/853/files/856_etd.pdf
L4  - https://digitalcollections.ohsu.edu/record/853/files/856_etd.pdf
LK  - https://digitalcollections.ohsu.edu/record/853/files/856_etd.pdf
N2  - Slow 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.
PB  - Oregon Health and Science University
PY  - 2012
T1  - Self repair in a zebrafish model for slow-channel myasthenic syndrome
TI  - Self repair in a zebrafish model for slow-channel myasthenic syndrome
UR  - https://digitalcollections.ohsu.edu/record/853/files/856_etd.pdf
Y1  - 2012
ER  -