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The Journal of Neuroscience, February 11, 2004, 24(6):1296-1304; doi:10.1523/JNEUROSCI.3560-03.2004

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Cellular/Molecular
Circadian Regulation of cGMP-Gated Channels of Vertebrate Cone Photoreceptors: Role of cAMP and Ras

Gladys Y.-P. Ko, Michael L. Ko, and Stuart E. Dryer

Department of Biology and Biochemistry and Biological Clocks Program, University of Houston, Houston, Texas 77204-5001

Circadian oscillators in chicken cone photoreceptors regulate the gating properties of cGMP-gated cationic channels (CNGCs) such that they have a higher apparent affinity for cGMP during the subjective night. Here we show that cAMP, acting through protein kinase A (PKA), Ras, and Erk, is part of the circadian output pathway controlling CNGCs. Endogenous and exogenous cAMP cause activation of Erk and Ras, which are more active at night in cones, and increase the apparent affinity of CNGCs for cGMP. The Ras farnesyl transferase inhibitor manumycin-A, and a dominant-negative form of Ras (RasN17) block the circadian rhythms in CNGC gating, as well as the effects of cAMP. A dominant-negative form of the MEK kinase B-Raf also blocks circadian and cAMP modulation of CNGCs. The circadian output pathway modulating CNGC channels is comprised in part of cAMP PKA Ras B-Raf MEK Erk CNGCs. cAMP activation of Ras and Erk occur within minutes, whereas modulation of CNGCs requires >1 hr. However, cAMP protagonists do not alter rhythms in cPer2 mRNA, and their effects on CNGCs cannot be attributed to clock phase-shifting.

Key words: circadian; phototransduction; ERK; Ras; cAMP; channel; Raf

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Received July 30, 2003; revised December 11, 2003; accepted December 15, 2003.

This article has been cited by other articles:

				M. L. Ko, Y. Liu, L. Shi, D. Trump, and G. Y.-P. Ko Circadian Regulation of Retinoschisin in the Chick Retina Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1615 - 1621. [Abstract] [Full Text] [PDF]

				M. V. Podda, M. D'Ascenzo, L. Leone, R. Piacentini, G. B. Azzena, and C. Grassi Functional role of cyclic nucleotide-gated channels in rat medial vestibular nucleus neurons J. Physiol., February 1, 2008; 586(3): 803 - 815. [Abstract] [Full Text] [PDF]

				S.-K. Chen, G. Y.-P. Ko, and S. E. Dryer Somatostatin Peptides Produce Multiple Effects on Gating Properties of Native Cone Photoreceptor cGMP-Gated Channels That Depend on Circadian Phase and Previous Illumination J. Neurosci., November 7, 2007; 27(45): 12168 - 12175. [Abstract] [Full Text] [PDF]

				C.-J. Yu, Y. Gao, P. Li, and L. Li Synchronizing multiphasic circadian rhythms of rhodopsin promoter expression in rod photoreceptor cells J. Exp. Biol., February 15, 2007; 210(4): 676 - 684. [Abstract] [Full Text] [PDF]

				K.-S. Chae, G. Y.-P. Ko, and S. E. Dryer Tyrosine Phosphorylation of cGMP-Gated Ion Channels Is under Circadian Control in Chick Retina Photoreceptors Invest. Ophthalmol. Vis. Sci., February 1, 2007; 48(2): 901 - 906. [Abstract] [Full Text] [PDF]

				P. Li, S. Temple, Y. Gao, T. J. Haimberger, C. W. Hawryshyn, and L. Li Circadian rhythms of behavioral cone sensitivity and long wavelength opsin mRNA expression: a correlation study in zebrafish J. Exp. Biol., February 1, 2005; 208(3): 497 - 504. [Abstract] [Full Text] [PDF]

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