title: Circadian phase-dependent effect of nitric oxide on L-type voltage-gated calcium channels in avian cone photoreceptors.
abstract: Nitric oxide (NO) plays an important role in phase-shifting of circadian neuronal activities in the suprachiasmatic nucleus and circadian behavior activity rhythms. In the retina, NO production is increased in a light-dependent manner. While endogenous circadian oscillators in retinal photoreceptors regulate their physiological states, it is not clear whether NO also participates in the circadian regulation of photoreceptors. In this study, we demonstrate that NO is involved in the circadian phase-dependent regulation of L-type voltage-gated calcium channels (L-VGCCs). In chick cone photoreceptors, the L-VGCCα1 subunit expression and the maximal L-VGCC currents are higher at night, and both Ras-mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (Erk) and Ras-phosphatidylinositol 3 kinase (PI3K)-protein kinase B (Akt) are part of the circadian output pathways regulating L-VGCCs. The NO-cGMP-protein kinase G (PKG) pathway decreases L-VGCCα1 subunit expression and L-VGCC currents at night, but not during the day, and exogenous NO donor or cGMP decreases the phosphorylation of Erk and Akt at night. The protein expression of neural NO synthase (nNOS) is also under circadian control, with both nNOS and NO production being higher during the day. Taken together, NO/cGMP/PKG signaling is involved as part of the circadian output pathway to regulate L-VGCCs in cone photoreceptors. In cone photoreceptors, the protein expression of neural nitric oxide synthase (nNOS) and NO production are under circadian control. NO-cGMP-protein kinase G (PKG) signaling serves in the circadian output pathway to regulate the circadian rhythms of L-type voltage-gated calcium channels (L-VGCCs) in part through regulating the phosphorylation states of extracellular-signal-regulated kinase (Erk) and protein kinase B (Akt).
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Ko
authors.forename: Liheng
authors.initials: L
authors.lastname: Shi
authors.forename: Cathy C-Y
authors.initials: CC
authors.lastname: Huang
authors.forename: Kirill
authors.initials: K
authors.lastname: Grushin
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Gladys Y-P
authors.initials: GY
authors.lastname: Ko
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002642:Chick Embryo; D002940:Circadian Rhythm / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000502:physiology; D018408:Patch-Clamp Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
chemical_list: D020746:Calcium Channels, L-Type; D009566:Nitrates; D020030:Nitric Oxide Donors; D034741:RNA, Small Interfering; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP
keywords: circadian; cone; ion channel; photoreceptor; retina; signaling
references.citation: Free Radic Biol Med. 2011 Jul 1;51(1):17-29
references.pmid: 21549190
references.citation: J Neurophysiol. 2004 Jul;92(1):477-83
references.pmid: 14985410
references.citation: Vis Neurosci. 1992 Apr;8(4):315-27
references.pmid: 1314087
references.citation: Nature. 1988 Jul 7;334(6177):64-6
references.pmid: 2455233
references.citation: Neuron. 1993 Apr;10(4):579-84
references.pmid: 8476610
references.citation: Circ Res. 2008 Mar 14;102(5):607-14
references.pmid: 18218984
references.citation: Science. 1994 Dec 9;266(5191):1713-7
references.pmid: 7527589
references.citation: Vis Neurosci. 2001 Nov-Dec;18(6):949-60
references.pmid: 12020086
references.citation: FASEB J. 1999 Dec;13(15):2143-52
references.pmid: 10593861
references.citation: Biochem J. 2006 Jul 15;397(2):329-36
references.pmid: 16569214
references.citation: Am J Physiol Regul Integr Comp Physiol. 2001 May;280(5):R1348-55
references.pmid: 11294753
references.citation: Neuron. 1994 Jun;12(6):1345-52
references.pmid: 7912093
references.citation: Inflammopharmacology. 2011 Apr;19(2):89-97
references.pmid: 21279549
references.citation: J Neurophysiol. 2007 Feb;97(2):1188-95
references.pmid: 17182910
references.citation: J Comp Neurol. 2000 Jan 10;416(2):269-75
references.pmid: 10581471
references.citation: J Neurophysiol. 1997 Jun;77(6):3075-84
references.pmid: 9212258
references.citation: PLoS One. 2009;4(1):e4238
references.pmid: 19156199
references.citation: Nature. 1989 Feb 2;337(6206):454-7
references.pmid: 2521689
references.citation: Vis Neurosci. 2003 Jul-Aug;20(4):453-63
references.pmid: 14658773
references.citation: Neurosci Lett. 1995 Jun 2;192(1):25-8
references.pmid: 7675302
references.citation: PLoS One. 2012;7(11):e50602
references.pmid: 23189207
references.citation: Prog Brain Res. 2001;131:477-85
references.pmid: 11420964
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Feb;294(2):R487-93
references.pmid: 18046020
references.citation: J Neurochem. 2009 Aug;110(4):1150-69
references.pmid: 19549279
references.citation: J Cell Biochem. 2012 Mar;113(3):911-22
references.pmid: 22371971
references.citation: Neuroreport. 1997 Dec 1;8(17):3763-6
references.pmid: 9427366
references.citation: Vision Res. 2011 Jan;51(1):131-7
references.pmid: 20951158
references.citation: Pharmacol Rev. 2005 Dec;57(4):411-25
references.pmid: 16382099
references.citation: Invest Ophthalmol Vis Sci. 1980 Apr;19(4):407-11
references.pmid: 7358492
references.citation: Invest Ophthalmol Vis Sci. 2007 Feb;48(2):901-6
references.pmid: 17251493
references.citation: J Cell Sci. 2003 Jan 1;116(Pt 1):9-15
references.pmid: 12456711
references.citation: Eur J Pharmacol. 2010 May 10;633(1-3):1-9
references.pmid: 20149790
references.citation: Biochemistry. 2004 Mar 2;43(8):2314-22
references.pmid: 14979728
references.citation: Brain Res. 2004 Sep 24;1021(2):277-80
references.pmid: 15342277
references.citation: J Neurochem. 2007 Oct;103(2):784-92
references.pmid: 17683482
references.citation: Neurosci Lett. 2003 Oct 23;350(2):122-6
references.pmid: 12972168
references.citation: Antioxid Redox Signal. 2013 Jan 20;18(3):221-38
references.pmid: 22894707
references.citation: Mol Pharmacol. 2005 Oct;68(4):1006-17
references.pmid: 16027232
references.citation: J Biol Chem. 1998 Feb 13;273(7):4220-6
references.pmid: 9461619
references.citation: Adv Exp Med Biol. 2002;514:465-76
references.pmid: 12596939
references.citation: Neurosci Lett. 2000 Oct 13;292(3):220-2
references.pmid: 11018316
references.citation: J Biol Chem. 2009 Feb 6;284(6):3966-75
references.pmid: 19074145
references.citation: J Gen Physiol. 1985 Nov;86(5):671-89
references.pmid: 2999294
references.citation: Science. 1983 Mar 18;219(4590):1341-3
references.pmid: 6828862
references.citation: Neurochem Int. 2004 Nov;45(6):929-36
references.pmid: 15312987
references.citation: J Neurochem. 2009 Mar;108(6):1607-20
references.pmid: 19166512
references.citation: Physiol Genomics. 2007 May 11;29(3):280-9
references.pmid: 17284666
references.citation: FEBS Lett. 2007 Nov 27;581(28):5500-4
references.pmid: 17991439
references.citation: Pflugers Arch. 2010 May;459(6):807-16
references.pmid: 20082095
references.citation: Neurosci Lett. 1995 Sep 15;197(3):227-30
references.pmid: 8552305
references.citation: Proc Natl Acad Sci U S A. 1998 May 12;95(10):5773-8
references.pmid: 9576960
references.citation: Biochem J. 2001 Aug 1;357(Pt 3):593-615
references.pmid: 11463332
references.citation: J Neurophysiol. 2006 Oct;96(4):2025-33
references.pmid: 16738212
references.citation: Invest Ophthalmol Vis Sci. 1999 Sep;40(10):2165-72
references.pmid: 10476779
references.citation: J Biol Chem. 2009 Sep 18;284(38):25791-803
references.pmid: 19608742
references.citation: Brain Res. 2005 Jul 19;1050(1-2):101-9
references.pmid: 15978557
references.citation: J Neurosci. 2004 Feb 11;24(6):1296-304
references.pmid: 14960600
references.citation: Biochem Cell Biol. 1992 Oct-Nov;70(10-11):1277-82
references.pmid: 1338414
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11788-93
references.pmid: 19556550
references.citation: Neuroreport. 2002 Dec 3;13(17):2247-51
references.pmid: 12488805
references.citation: Brain Res. 1995 Sep 18;692(1-2):137-42
references.pmid: 8548297
references.citation: Neuron. 2001 Jan;29(1):255-66
references.pmid: 11182096
references.citation: J Biol Rhythms. 2004 Apr;19(2):91-102
references.pmid: 15038849
references.citation: J Biol Chem. 2005 Mar 4;280(9):7511-8
references.pmid: 15632167
references.citation: J Biol Rhythms. 1997 Aug;12(4):319-26
references.pmid: 9438880