PT  - JOURNAL ARTICLE
AU  - Luciano Marpegan
AU  - Adrienne E. Swanstrom
AU  - Kevin Chung
AU  - Tatiana Simon
AU  - Philip G. Haydon
AU  - Sanjoy K. Khan
AU  - Andrew C. Liu
AU  - Erik D. Herzog
AU  - Christian Beaulé
TI  - Circadian Regulation of ATP Release in Astrocytes
AID  - 10.1523/JNEUROSCI.6537-10.2011
DP  - 2011 Jun 08
TA  - The Journal of Neuroscience
PG  - 8342--8350
VI  - 31
IP  - 23
4099  - http://www.jneurosci.org/content/31/23/8342.short
4100  - http://www.jneurosci.org/content/31/23/8342.full
SO  - J. Neurosci.2011 Jun 08; 31
AB  - Circadian clocks sustain daily oscillations in gene expression, physiology, and behavior, relying on transcription–translation feedback loops of clock genes for rhythm generation. Cultured astrocytes display daily oscillations of extracellular ATP, suggesting that ATP release is a circadian output. We hypothesized that the circadian clock modulates ATP release via mechanisms that regulate acute ATP release from glia. To test the molecular basis for circadian ATP release, we developed methods to measure in real-time ATP release and Bmal1::dLuc circadian reporter expression in cortical astrocyte cultures from mice of different genotypes. Daily rhythms of gene expression required functional Clock and Bmal1, both Per1 and Per2, and both Cry1 and Cry2 genes. Similarly, high-level, circadian ATP release also required a functional clock mechanism. Whereas blocking IP3 signaling significantly disrupted ATP rhythms with no effect on Bmal1::dLuc cycling, blocking vesicular release did not alter circadian ATP release or gene expression. We conclude that astrocytes depend on circadian clock genes and IP3 signaling to express daily rhythms in ATP release.