Intracellular calcium as a clock output from scn neurons

Abstract

In mammals, the major circadian clock is located in the suprachiasmatic nuclei (SCN). The molecular oscillator in these neurons is driven by transcriptional- translational feedback loops (TTL) among clock genes that generate a circadian periodicity. To fulfill its role as pacemaker, the molecular oscillation must be translated to an electrical signal in SCN neurons, which will be transmitted to the rest of the brain and eventually the organism. The mechanisms involved in this process remain mostly unknown, but some information is already available. Among the ion channels in SCN neurons which are regulated by the circadian clock, only the manipulations of the fast delayed rectifier (fDR) and large-conductance (BK) K + currents have shown to affect circadian rhythmicity either in neuronal firing pattern or behavior. On the other hand, data from rat and mouse clearly indicate that intracellular Ca 2+ channels sensitive to ryanodine (RyR) are part of an output pathway of the clock in SCN neurons. Intracellular Ca 2+ signals mediate between the molecular circadian clock and the neuronal plasma membrane of SCN neurons and thus can modulate the excitability and firing frequency according to the time of day. Intracellular Ca 2+ mobilization through RyRs may affect neuronal excitability directly through Ca 2+ -modulated plasma membrane channels and indirectly as a second messenger activating protein kinases regulating a variety of cellular processes converging at the cell membrane.