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Full-Text Articles in Physiology
Cardiomyocyte Deletion Of Bmal1 Exacerbates Qt- And Rr-Interval Prolongation In Scn5a+/Δkpq Mice, Elizabeth A. Schroder, Jennifer L. Wayland, Kaitlyn M. Samuels, Syed F. Shah, Don E. Burgess, Tanya S. Seward, Claude S. Elayi, Karyn A. Esser, Brian P. Delisle
Cardiomyocyte Deletion Of Bmal1 Exacerbates Qt- And Rr-Interval Prolongation In Scn5a+/Δkpq Mice, Elizabeth A. Schroder, Jennifer L. Wayland, Kaitlyn M. Samuels, Syed F. Shah, Don E. Burgess, Tanya S. Seward, Claude S. Elayi, Karyn A. Esser, Brian P. Delisle
Physiology Faculty Publications
Circadian rhythms are generated by cell autonomous circadian clocks that perform a ubiquitous cellular time-keeping function and cell type-specific functions important for normal physiology. Studies show inducing the deletion of the core circadian clock transcription factor Bmal1 in adult mouse cardiomyocytes disrupts cardiac circadian clock function, cardiac ion channel expression, slows heart rate, and prolongs the QT-interval at slow heart rates. This study determined how inducing the deletion of Bmal1 in adult cardiomyocytes impacted the in vivo electrophysiological phenotype of a knock-in mouse model for the arrhythmogenic long QT syndrome (Scn5a+/ΔKPQ). Electrocardiographic telemetry showed inducing the …
Long Qt Syndrome Type 2: Emerging Strategies For Correcting Class 2 Kcnh2 (Herg) Mutations And Identifying New Patients, Makoto Ono, Don E. Burgess, Elizabeth A. Schroder, Claude S. Elayi, Corey L. Anderson, Craig T. January, Bin Sun, Kalyan Immadisetty, Peter M. Kekenes-Huskey, Brian P. Delisle
Long Qt Syndrome Type 2: Emerging Strategies For Correcting Class 2 Kcnh2 (Herg) Mutations And Identifying New Patients, Makoto Ono, Don E. Burgess, Elizabeth A. Schroder, Claude S. Elayi, Corey L. Anderson, Craig T. January, Bin Sun, Kalyan Immadisetty, Peter M. Kekenes-Huskey, Brian P. Delisle
Physiology Faculty Publications
Significant advances in our understanding of the molecular mechanisms that cause congenital long QT syndrome (LQTS) have been made. A wide variety of experimental approaches, including heterologous expression of mutant ion channel proteins and the use of inducible pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from LQTS patients offer insights into etiology and new therapeutic strategies. This review briefly discusses the major molecular mechanisms underlying LQTS type 2 (LQT2), which is caused by loss-of-function (LOF) mutations in the KCNH2 gene (also known as the human ether-à-go-go-related gene or hERG). Almost half of suspected LQT2-causing mutations are missense mutations, and functional studies …
Visualizing Mutation-Specific Differences In The Trafficking-Deficient Phenotype Of Kv11.1 Proteins Linked To Long Qt Syndrome Type 2, Allison R. Hall, Corey L. Anderson, Jennifer L. Smith, Tooraj Mirshahi, Samy-Claude Elayi, Craig T. January, Brian P. Delisle
Visualizing Mutation-Specific Differences In The Trafficking-Deficient Phenotype Of Kv11.1 Proteins Linked To Long Qt Syndrome Type 2, Allison R. Hall, Corey L. Anderson, Jennifer L. Smith, Tooraj Mirshahi, Samy-Claude Elayi, Craig T. January, Brian P. Delisle
Physiology Faculty Publications
KCNH2 encodes the Kv11.1 α-subunit that underlies the rapidly activating delayed-rectifier K+ current in the heart. Loss-of-function KCNH2 mutations cause long QT syndrome type 2 (LQT2), and most LQT2-linked missense mutations inhibit the trafficking of Kv11.1 channel protein to the cell surface membrane. Several trafficking-deficient LQT2 mutations (e.g., G601S) generate Kv11.1 proteins that are sequestered in a microtubule-dependent quality control (QC) compartment in the transitional endoplasmic reticulum (ER). We tested the hypothesis that the QC mechanisms that regulate LQT2-linked Kv11.1 protein trafficking are mutation-specific. Confocal imaging analyses of HEK293 cells stably expressing the trafficking-deficient LQT2 mutation F805C showed that, …