Minding the gaps that link intrinsic circadian clock within the heart to its intrinsic ultradian pacemaker clocks. Focus on "The cardiomyocyte molecular clock, regulation of Scn5a, and arrhythmia susceptibility".

A hierarchical system of clocks within cells throughout the body creates and synchronizes rhythmic functions from which life emerges. Biological circadian rhythms, linked to light and darkness in an organism’s environment, are generated by transcription-translation feedback mechanisms on universal “core” clock genes, e.g., Clock, Bmal1, Per1, Per2, Cry1 and Cry2 (16). Clocks within the brain broadcast signals to all tissues (5). Many cell types also exhibit their “local” circadian clocks, as well as infradian and ultradian clocks that rhythmically regulate cell type-specific functions on time scales commensurate with the functions. Functional regulation by clocks range from activation-inactivation-reactivation cycles of molecules (e.g., ion channels) at millisecond scales, the heart’s beating at cycles of hundreds of milliseconds, respiration at cycle of seconds, low-frequency autonomic signaling at cycles of tens of seconds, to diurnal and infradian variations of numerous body functions.