BIO411H5 Lecture Notes - Lecture 1: Telemetry, Electrophysiology, Cardiac Electrophysiology
Document Summary
The molecular basis that links circadian rhythms to vulnerability in ventricular arrhythmias eventually leading to cardiac death is unknown. Both abnormalities in the duration and pattern of myocardial repolarization are mechanisms leading to ventricular arrhythmias. The focus of this paper is kr ppel-like factor 15 (klf15) which is observed to have endogenous circadian rhythmicity in the heart. Gene expression microarray in klf-15 deficient hearts of mice identifies the rhythmic expression of kv channel-interacting protein 2 (kchip2), a regulatory b-subunit for the repolarizing transient outward potassium current (ito). Further examination by chromatin immunoprecipitation (chip) reveals klf15 has 4 canonical e-box binding sites for clock and bmal1 in the hearts of mice. Deleting bmal1, per2, or cry1 disrupted expression of klf15 thus strongly suggesting that oscillation of klf15 is regulated by the circadian clock. Endogenous rhythmicity of klf15 is examined by the observation of kv4. 2 (encoded by kcnd2) and kchip2. It is found that both regulatory subunits are rhythmic.
