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 the present 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-MAPK (mitogen-activated protein kinase)-Erk (extracellular-signal-regulated kinase) 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.

Pattern of nitrergic cells and fibers organization in the central nervous system of the Australian lungfish,Neoceratodus forsteri(Sarcopterygii: Dipnoi)

“…Furthermore, nitrergic bipolar neurons have been detected in the retina of Chondrichthyes (Shiells & Falk, ), amphibians (Blom et al, ; Kurenni et al, ; Nöll et al, ), and reptiles (Cao & Eldred, ), whereas horizontal nitrergic cells have been reported only in teleosts (Haamedi & Djamgoz, ; Ota et al, ) and reptiles (Cuenca et al, ; Haverkamp & Eldred, ). This diversity suggests additional functions of NO in the retina such as light‐adaptive changes (Angotzi, Hirano, Vallerga, & Djamgoz, ; Djamgoz et al, ; Greenstreet & Djamgoz, ; Sato, Ohtsuka, & Stell, ) or circadian effect in the photoreceptor activity (Ko et al, ).…”

Organization of the nitrergic neuronal system in the primitive bony fishesPolypterus senegalusandErpetoichthys calabaricus(Actinopterygii: Cladistia)

“…In addition, nitrergic bipolar cells have been reported for chondrichthyes (Shiells and Falk, ), amphibians (Nöll et al, ; Kurenni et al, ; Blom et al, ), and reptiles (Cao and Eldred, ), whereas horizontal nitrergic cells have been described only for teleosts (Ota et al, ; Haamedi and Djamgoz, ) and reptiles (Haverkamp and Eldred, ; Cuenca et al, ). This increased diversity of nitrergic retinal types observed in more evolved groups of vertebrates could be related to new functions of NO in the retina such as light‐adaptive changes (Greenstreet and Djamgoz, ; Djamgoz et al, ; Angotzi et al, ; Sato et al, ) or circadian effects in photoreceptor activity (Ko et al, ).…”

Circadian regulation in the retina: From molecules to network

“…Among retinal cells, the circadian oscillation in photoreceptors is studied the most (Baba, Ribelayga, Michael Iuvone, & Tosini, ; Burnside, Evans, Fletcher, & Chader, ; Cahill & Besharse, , ; Chaurasia, Haque, Pozdeyev, Jackson, & Iuvone, ; Fisher, Pfeffer, & Anderson, ; Green & Besharse, ; Haque et al., ; Hasegawa & Cahill, , 1999a, 1999b, ; Ivanova, Alonso‐Gomez, & Iuvone, ; Jackson et al., ; Jin, Chuang, Masson, & Ribelayga, ; Ko, Ko, & Dryer, , , 2004a; Ko et al., ; Ko, Liu, Dryer, & Ko, ; Ko, Jian, Shi, & Ko, ; Ko et al., ; LaVail, ; Li et al., ; Manglapus et al., ; Menger, Koke, & Cahill, ; Menger et al., ; Pierce & Besharse, , ; Pierce et al., ; Ribelayga, Cao, & Mangel, ; Sakamoto, Liu, Kasamatsu, Iuvone, & Tosini, ; Stenkamp, Iuvone, & Adler, ; Tosini, Davidson, Fukuhara, Kasamatsu, & Castanon‐Cervantes, ; Valenciano, Alonso‐Gomez, & Iuvone, ; Young, ; Zhang, Li, Liu, O'Brien, & Ribelayga, ). Rod and cone photoreceptors are the first neurons to detect light and relay this information to the bipolar cells and then to ganglion cells for vision.…”