Retinal Bipolar Neurons Express the Cyclic Nucleotide-Gated Channel of Cone Photoreceptors

2003 ◽  
Vol 89 (2) ◽  
pp. 754-761 ◽  
Author(s):  
Diane Henry ◽  
Stephanie Burke ◽  
Emiko Shishido ◽  
Gary Matthews
Keyword(s):  
Nitric Oxide ◽  
Single Cell ◽  
Cyclic Nucleotide ◽  
Bipolar Cells ◽  
Cone Photoreceptors ◽  
Nitric Oxide Signaling ◽  
Cng Channel ◽  
Gated Channel ◽  
Goldfish Retina

Cyclic nucleotide-gated (CNG) channels link intracellular cyclic nucleotides to changes in membrane ionic conductance in a variety of physiological contexts. In the retina, in addition to their central role in phototransduction, CNG channels may be involved in nitric oxide signaling in bipolar neurons or in the hyperpolarizing synaptic response to glutamate inon-type (depolarizing) bipolar cells. Despite their potential physiological significance, however, expression of CNG channels has not yet been demonstrated in bipolar cells. To identify CNG channel subtypes in retinal bipolar neurons, we used single-cell molecular biological techniques in morphologically distinctiveon bipolar cells from goldfish retina. Both single-cell in situ hybridization and single-cell RT-PCR demonstrated inon bipolar cells the presence of mRNA for the CNG channel subtype that is also found in cone photoreceptors. Other bipolar cells, which likely represent off cells, did not express the cone CNG channel. Thus the CNG channel of cone photoreceptors is expressed in on bipolar cells, where it may be involved in physiological responses to nitric oxide, or in the sign-inverting glutamatergic synapse that gives rise to the on visual pathway.

scholarly journals Odorant Inhibition of the Olfactory Cyclic Nucleotide-gated Channel with a Native Molecular Assembly

2006 ◽  
Vol 128 (3) ◽  
pp. 365-371 ◽  
Author(s):  
Tsung-Yu Chen ◽  
Hiroko Takeuchi ◽  
Takashi Kurahashi
Keyword(s):  
Cyclic Nucleotide ◽  
Inhibitory Effect ◽  
Molecular Assembly ◽  
Definitive Evidence ◽  
Wide Range ◽  
Cng Channel ◽  
Gated Channel ◽  
Receptor Neurons ◽  
G Protein Coupled ◽  
Fine Tune

Human olfaction comprises the opposing actions of excitation and inhibition triggered by odorant molecules. In olfactory receptor neurons, odorant molecules not only trigger a G-protein–coupled signaling cascade but also generate various mechanisms to fine tune the odorant-induced current, including a low-selective odorant inhibition of the olfactory signal. This wide-range olfactory inhibition has been suggested to be at the level of ion channels, but definitive evidence is not available. Here, we report that the cyclic nucleotide-gated (CNG) cation channel, which is a key element that converts odorant stimuli into electrical signals, is inhibited by structurally unrelated odorants, consistent with the expression of wide-range olfactory inhibition. Interestingly, the inhibitory effect was small in the homo-oligomeric CNG channel composed only of the principal channel subunit, CNGA2, but became larger in channels consisting of multiple types of subunits. However, even in the channel containing all native subunits, the potency of the suppression on the cloned CNG channel appeared to be smaller than that previously shown in native olfactory neurons. Nonetheless, our results further showed that odorant suppressions are small in native neurons if the subsequent molecular steps mediated by Ca2+ are removed. Thus, the present work also suggests that CNG channels switch on and off the olfactory signaling pathway, and that the on and off signals may both be amplified by the subsequent olfactory signaling steps.

Molecular Characterization and In Situ Localization Of A Full-Length Cyclic Nucleotide-Gated Channel In Rat Brain

1999 ◽  
Vol 11 (12) ◽  
pp. 4463-4467 ◽  
Author(s):  
Paul J. L. M. Strijbos ◽  
Gerard D. Pratt ◽  
Shahid Khan ◽  
Ian G. Charles ◽  
John Garthwaite
Keyword(s):  
Rat Brain ◽  
Molecular Characterization ◽  
Cyclic Nucleotide ◽  
Full Length ◽  
Gated Channel

scholarly journals cGMP/Protein Kinase G Signaling Suppresses Inositol 1,4,5-Trisphosphate Receptor Phosphorylation and Promotes Endoplasmic Reticulum Stress in Photoreceptors of Cyclic Nucleotide-gated Channel-deficient Mice

2015 ◽  
Vol 290 (34) ◽  
pp. 20880-20892 ◽  
Author(s):  
Hongwei Ma ◽  
Michael R. Butler ◽  
Arjun Thapa ◽  
Josh Belcher ◽  
Fan Yang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Er Stress ◽  
Cyclic Nucleotide ◽  
Protein Kinase G ◽  
Cng Channel ◽  
Inositol 1,4,5 Trisphosphate ◽  
Gated Channel ◽  
Trisphosphate Receptor ◽  
Deficient Mice

Photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in phototransduction. Mutations in the cone CNG channel subunits CNGA3 and CNGB3 are associated with achromatopsia and cone dystrophies. We have shown endoplasmic reticulum (ER) stress-associated apoptotic cone death and increased phosphorylation of the ER Ca2+ channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) in CNG channel-deficient mice. We also presented a remarkable elevation of cGMP and an increased activity of the cGMP-dependent protein kinase (protein kinase G, PKG) in CNG channel deficiency. This work investigated whether cGMP/PKG signaling regulates ER stress and IP3R1 phosphorylation in CNG channel-deficient cones. Treatment with PKG inhibitor and deletion of guanylate cyclase-1 (GC1), the enzyme producing cGMP in cones, were used to suppress cGMP/PKG signaling in cone-dominant Cnga3−/−/Nrl−/− mice. We found that treatment with PKG inhibitor or deletion of GC1 effectively reduced apoptotic cone death, increased expression levels of cone proteins, and decreased activation of Müller glial cells. Furthermore, we observed significantly increased phosphorylation of IP3R1 and reduced ER stress. Our findings demonstrate a role of cGMP/PKG signaling in ER stress and ER Ca2+ channel regulation and provide insights into the mechanism of cone degeneration in CNG channel deficiency.

scholarly journals β Subunits of the Olfactory Cyclic Nucleotide-Gated Channel Form a Nitric Oxide Activated Ca2+ Channel

Neuron ◽  
1997 ◽  
Vol 18 (6) ◽  
pp. 951-958 ◽  
Author(s):  
Marie-Christine Broillet ◽  
Stuart Firestein
Keyword(s):  
Nitric Oxide ◽  
Cyclic Nucleotide ◽  
Channel Form ◽  
Gated Channel

Nitric oxide release from a single cell measured in situ by a porphyrinic-based microsensor

Nature ◽  
1992 ◽  
Vol 358 (6388) ◽  
pp. 676-678 ◽  
Author(s):  
Tadeusz Malinski ◽  
Ziad Taha
Keyword(s):  
Nitric Oxide ◽  
Single Cell ◽  
Nitric Oxide Release

scholarly journals Natriuretic Peptides and Nitric Oxide Stimulate cGMP Synthesis in Different Cellular Compartments

2006 ◽  
Vol 128 (1) ◽  
pp. 3-14 ◽  
Author(s):  
Leslie A. Piggott ◽  
Kathryn A. Hassell ◽  
Zuzana Berkova ◽  
Andrew P. Morris ◽  
Michael Silberbach ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Cyclic Nucleotide ◽  
Phosphodiesterase Inhibitor ◽  
Soluble Guanylyl Cyclase ◽  
Nitric Oxide Donor ◽  
Dependent Manner ◽  
Channel Activity ◽  
Hek 293 ◽  
Cng Channel

Cyclic nucleotide-gated (CNG) channels are a family of ion channels activated by the binding of cyclic nucleotides. Endogenous channels have been used to measure cyclic nucleotide signals in photoreceptor outer segments and olfactory cilia for decades. Here we have investigated the subcellular localization of cGMP signals by monitoring CNG channel activity in response to agonists that activate either particulate or soluble guanylyl cyclase. CNG channels were heterologously expressed in either human embryonic kidney (HEK)-293 cells that stably overexpress a particulate guanylyl cyclase (HEK-NPRA cells), or cultured vascular smooth muscle cells (VSMCs). Atrial natriuretic peptide (ANP) was used to activate the particulate guanylyl cyclase and the nitric oxide donor S-nitroso-n-acetylpenicillamine (SNAP) was used to activate the soluble guanylyl cyclase. CNG channel activity was monitored by measuring Ca2+ or Mn2+ influx through the channels using the fluorescent dye, fura-2. We found that in HEK-NPRA cells, ANP-induced increases in cGMP levels activated CNG channels in a dose-dependent manner (0.05–10 nM), whereas SNAP (0.01–100 μM) induced increases in cGMP levels triggered little or no activation of CNG channels (P < 0.01). After pretreatment with 100 μM 3-isobutyl-1-methylxanthine (IBMX), a nonspecific phosphodiesterase inhibitor, ANP-induced Mn2+ influx through CNG channels was significantly enhanced, while SNAP-induced Mn2+ influx remained small. In contrast, we found that in the presence of IBMX, both 1 nM ANP and 100 μM SNAP triggered similar increases in total cGMP levels. We next sought to determine if cGMP signals are compartmentalized in VSMCs, which endogenously express particulate and soluble guanylyl cyclase. We found that 10 nM ANP induced activation of CNG channels more readily than 100 μM SNAP; whereas 100 μM SNAP triggered higher levels of total cellular cGMP accumulation. These results suggest that cGMP signals are spatially segregated within cells, and that the functional compartmentalization of cGMP signals may underlie the unique actions of ANP and nitric oxide.

NO upregulation of a cyclic nucleotide-gated channel contributes to calcium elevation in endothelial cells

2002 ◽  
Vol 283 (4) ◽  
pp. C1080-C1089 ◽  
Author(s):  
Jianliang Zhang ◽  
Shen-Ling Xia ◽  
Edward R. Block ◽  
Jawaharlal M. Patel
Keyword(s):  
Endothelial Cells ◽  
Cyclic Nucleotide ◽  
Cytosolic Calcium ◽  
Calcium Entry ◽  
Mrna Levels ◽  
No Donor ◽  
Cng Channel ◽  
Gated Channel ◽  
Calcium Elevation ◽  
Porcine Pulmonary Artery

We investigated whether nitric oxide (NO) upregulates a cyclic nucleotide-gated (CNG) channel and whether this contributes to sustained elevation of intracellular calcium levels ([Ca2+]i) in porcine pulmonary artery endothelial cells (PAEC). Exposure of PAEC to an NO donor, NOC-18 (1 mM), for 18 h increased the protein and mRNA levels of CNGA2 40 and 50%, respectively ( P < 0.05). [Ca2+]iin NO-treated cells was increased 50%, and this increase was maintained for up to 12 h after removal of NOC-18 from medium. Extracellular calcium is required for the increase in [Ca2+]iin NO-treated cells. Thapsigargin induced a rapid cytosolic calcium rise, whereas both a CNG and a nonselective cation channel blocker caused a faster decline in [Ca2+]i, suggesting that capacitive calcium entry contributes to the elevated calcium levels. Antisense inhibition of CNGA2 expression attenuated the NO-induced increases in CNGA2 expression and [Ca2+]iand in capacitive calcium entry. Our results demonstrate that exogenous NO upregulates CNGA2 expression and that this is associated with elevated [Ca2+]iand capacitive calcium entry in porcine PAEC.

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