טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentNovak-Petraro Atara
SubjectCellular and Molecular Mechanisms of Catecholaminergic
Polymorphic Ventricular Tachycardia (CPVT) in
Cardiomyocytes Generated from Induced
Pluripotent Stem Cells (iPSCs)
DepartmentDepartment of Medicine
Supervisors Professor Emeritus Ofer Binah
Professor Emeritus Joseph Itskovitz
Full Thesis textFull thesis text - English Version


Abstract

cytoplasmic Ca2 overload, but it is not the mechanism which induced triggered beats which probably originated from spontaneous SR Ca2 release during the diastole (SOICR). (2) Compared to healthy control iPSC-CM, caffeine release more Ca2 in CPVT2 iPSC-CM and less Ca2 in CPVT1 iPSC-CM. Additionally, while the control and CPVT1 iPSC-CM demonstrated prompt recovery after caffeine-induced SR Ca2 release, CPVT2 iPSC- CM demonstrated slower recovery. These findings may result from non-functional CASQ2 in CPVT2 iPSC-CM which causes uncontrolled Ca2 release via RyR2 channel, while CPVT1 iPSC-CM have unresponsive RyR2 channel which causes reduced Ca2 release. (3) In response to 10µM ryanodine, RyR blocker which locks the channel in a subconductance state, both CPVT1 and CPVT2 iPSC-CM caused increased cytoplasmic Ca2 levels, which might indicate a non-functional CRU.    

Our results show that the mutated cardiomyocytes can be used to investigate the electrophysiological mechanisms and the differences between the mutations in RYR2 and CASQ2 underlying CPVT.