Temporal coupling of cyclic AMP and Ca2+/CaM-stimulated adenylyl cyclase to the circadian clock in chick retinal photoreceptor cells

Cyclic AMP signaling pathways play crucial roles in photoreceptor cells and other retinal cell types. Previous studies demonstrated a circadian rhythm of cyclic AMP level in chick photoreceptor cell cultures that drives the rhythm of activity of the melatonin synthesizing enzyme arylalkylamine N-acetyltransferase ( Ivanova and Iuvone, 2003a ) and the rhythm of affinity of the cyclic nucleotide-gated channel for cyclic GMP ( Ko et al., 2004 ). Here we report that the photoreceptor circadian clock generates a rhythm in Ca 2+ /calmodulin-stimulated adenylyl cyclase activity, which accounts for the temporal changes in the cyclic AMP levels in the photoreceptors. The circadian rhythm of cyclic AMP in photoreceptor cell cultures is abolished by treatment with the L-type Ca 2+ channel antagonist nitrendipine, while the Ca 2+ channel agonist, Bay K 8644, increased cyclic AMP levels with continued circadian rhythmicity in constant darkness. These results indicate that the circadian rhythm of cyclic AMP is dependent, in part, on Ca 2+ influx. Photoreceptor cell cultures exhibit a circadian rhythm in Ca 2+ /calmodulin-stimulated adenylyl cyclase enzyme activity with high levels at night and low levels during the day, correlating with the temporal changes of cyclic AMP in these cells. Both of the Ca 2+ /calmodulin-stimulated adenylyl cyclase genes, type 1 and type 8 ( Adcy1 and Adcy8 ), displayed significant daily rhythms of mRNA expression under a light-dark cycle, but only the Adcy1 transcript rhythm persisted in constant darkness. Similar rhythms of Adcy1 mRNA level and Ca 2+ /calmodulin-stimulated adenylyl cyclase activity were observed in retinas of 2 week old chickens. These results indicate that a circadian clock controls the expression of Adcy1 mRNA and Ca 2+ /calmodulin-stimulated adenylyl cyclase activity; and calcium influx into these cells gates the circadian rhythm of cyclic AMP, a key component in the regulation of photoreceptor function.