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. 2014 Jun 20;20(18):2955–2965. doi: 10.1089/ars.2013.5598

FIG. 6.

FIG. 6.

Reciprocal interactions of the RXO, membrane excitability oscillator, and transcriptional–translational oscillator. (A) The RXO regulates the circadian rhythm of SCN neuronal activity by modulating opening of K+ channels (solid arrow) (79). Concomitantly, increased neuronal activity can increase blood flow, glucose uptake by astrocytes, and energy availability, which feeds back, modulating neuronal metabolic state (dashed arrow) (66). (B) Some ion channels that underlie membrane excitability are rhythmically expressed under the control of clock genes (solid arrow), although acute shifts in redox state can immediately alter membrane excitability (11, 13). At the same time, membrane excitability of SCN neurons gates signal input to the TTO, which in turn affects clock gene expression (dashed arrow) (22, 24, 45, 51). (C) The circadian oscillation of SCN redox state depends on a functional TTO (79). Redox state feeds back to the TTO, modulating clock gene expression (solid arrows) (5, 16, 59, 67). Adapted from Wang et al. (79).