The Cardiomyocyte Molecular Clock Augments K+ Channel Gene Expression to Safeguard Against a Large Circadian Oscillation in the QT Interval

摘要: Circadian rhythms are ~24-hour biological cycles that synchronize the timing of an organism’s physiology to daily changes. The mechanism that underlies circadian function is the molecular clock: a transcription-translation feedback loop comprised of the core clock genes Bmal1, Clock, Per1, Per2, Cry1 and Cry2. Studies with Bmal1-, Per2-, and Cry1-null mice suggest a link between the molecular clock, cardiac K+ channel expression, and ventricular repolarization. However, these studies do not distinguish between disruptions of the central clock in the brain vs. the molecular clock in the heart. We tested the role of the clock in the heart using a tamoxifen-induced cardiomyocyte-specific Bmal1 knockout mouse. We used real-time PCR to measure the expression of KCNA1, KCNA5, KCNB1, KCNQ1, KCNH2, and KCNJ2 in ventricular tissue isolated every 4 hours for 28 hours from vehicle-treated control (iCSBmal1 …