Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Movement of gating machinery during the activation of rod cyclic nucleotide-gated channels.
Brown RL
,
Snow SD
,
Haley TL
.
???displayArticle.abstract???
In the visual and olfactory systems, cyclic nucleotide-gated (CNG) ion channels convert stimulus-induced changes in the internal concentrations of cGMP and cAMP into changes in membrane potential. Although it is known that significant activation of these channels requires the binding of three or more molecules of ligand, the detailed molecular mechanism remains obscure. We have probed the structural changes that occur during channel activation by using sulfhydryl-reactive methanethiosulfonate (MTS) reagents and N-ethylmaleimide (NEM). When expressed in Xenopus oocytes, the alpha-subunit of the bovine retinal channel forms homomultimeric channels that are activated by cGMP with a K1/2 of approximately 100 microM. Cyclic AMP, on the other hand, is a very poor activator; a saturating concentration elicits only 1% of the maximum current produced by cGMP. Treatment of excised patches with MTS-ethyltrimethylamine (MTSET) or NEM dramatically potentiated the channel's response to both cyclic nucleotides. After MTSET treatment, the dose-response relation for cGMP was shifted by over two orders of magnitude to lower concentrations. The effect on channel activation by cAMP was even more striking. After modification, the channels were fully activated by cAMP with a K1/2 of approximately 60 microM. This potentiation was abolished by conversion of Cys481 to a nonreactive alanine residue. Potentiation occurred more rapidly in the presence of saturating cGMP, indicating that this region of the channel is more accessible when the channel is open. Cys481 is located in a linker region between the transmembrane and cGMP-binding domains of the channel. These results suggest that this region of the channel undergoes significant movement during the activation process and is critical for coupling ligand binding to pore opening. Potentiation, however, is not mediated by the recently reported interaction between the amino- and carboxy-terminal regions of the alpha-subunit. Deletion of the entire amino-terminal domain had little effect on potentiation by MTSET.
Akabas,
Identification of acetylcholine receptor channel-lining residues in the entire M2 segment of the alpha subunit.
1994, Pubmed,
Xenbase
Akabas,
Identification of acetylcholine receptor channel-lining residues in the entire M2 segment of the alpha subunit.
1994,
Pubmed
,
Xenbase
Akabas,
Identification of acetylcholine receptor channel-lining residues in the M1 segment of the alpha-subunit.
1995,
Pubmed
,
Xenbase
Biel,
Another member of the cyclic nucleotide-gated channel family, expressed in testis, kidney, and heart.
1994,
Pubmed
Broillet,
Direct activation of the olfactory cyclic nucleotide-gated channel through modification of sulfhydryl groups by NO compounds.
1996,
Pubmed
Brown,
Activation of retinal rod cGMP-gated channels: what makes for an effective 8-substituted derivative of cGMP?
1993,
Pubmed
Brown,
Cyclic GMP contact points within the 63-kDa subunit and a 240-kDa associated protein of retinal rod cGMP-activated channels.
1995,
Pubmed
Chen,
A new subunit of the cyclic nucleotide-gated cation channel in retinal rods.
1993,
Pubmed
,
Xenbase
Cook,
Identification, purification, and functional reconstitution of the cyclic GMP-dependent channel from rod photoreceptors.
1987,
Pubmed
Donner,
Sulfhydryl binding reagents increase the conductivity of the light-sensitive channel and inhibit phototransduction in retinal rods.
1990,
Pubmed
Feng,
Expression of photoreceptor cyclic nucleotide-gated cation channel alpha subunit (CNGCalpha) in the liver and skeletal muscle.
1996,
Pubmed
Finn,
Cyclic nucleotide-gated ion channels: an extended family with diverse functions.
1996,
Pubmed
Frings,
Profoundly different calcium permeation and blockage determine the specific function of distinct cyclic nucleotide-gated channels.
1995,
Pubmed
,
Xenbase
Gordon,
Localization of regions affecting an allosteric transition in cyclic nucleotide-activated channels.
1995,
Pubmed
,
Xenbase
Gordon,
Direct interaction between amino- and carboxyl-terminal domains of cyclic nucleotide-gated channels.
1997,
Pubmed
Goulding,
Molecular mechanism of cyclic-nucleotide-gated channel activation.
1994,
Pubmed
,
Xenbase
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Haynes,
Single cyclic GMP-activated channel activity in excised patches of rod outer segment membrane.
,
Pubmed
Henn,
Probing the transmembrane topology of cyclic nucleotide-gated ion channels with a gene fusion approach.
1995,
Pubmed
Jan,
Maggot's hair and bug's eye: role of cell interactions and intrinsic factors in cell fate specification.
1995,
Pubmed
Karpen,
Interactions between divalent cations and the gating machinery of cyclic GMP-activated channels in salamander retinal rods.
1993,
Pubmed
Kaupp,
Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel.
1989,
Pubmed
,
Xenbase
Kaupp,
Family of cyclic nucleotide gated ion channels.
1995,
Pubmed
Kingston,
Rat hippocampal neurons express genes for both rod retinal and olfactory cyclic nucleotide-gated channels: novel targets for cAMP/cGMP function.
1996,
Pubmed
Körschen,
A 240 kDa protein represents the complete beta subunit of the cyclic nucleotide-gated channel from rod photoreceptor.
1995,
Pubmed
Larsson,
Transmembrane movement of the shaker K+ channel S4.
1996,
Pubmed
,
Xenbase
Leinders-Zufall,
A calcium-permeable cGMP-activated cation conductance in hippocampal neurons.
1995,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Liu,
Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel.
1994,
Pubmed
Liu,
Subunit stoichiometry of cyclic nucleotide-gated channels and effects of subunit order on channel function.
1996,
Pubmed
Molday,
The cGMP-gated channel of the rod photoreceptor cell characterization and orientation of the amino terminus.
1991,
Pubmed
,
Xenbase
Rieke,
A cGMP-gated current can control exocytosis at cone synapses.
1994,
Pubmed
Ruiz,
Cloning and characterization of an olfactory cyclic nucleotide-gated channel expressed in mouse heart.
1996,
Pubmed
Ruiz,
Single cyclic nucleotide-gated channels locked in different ligand-bound states.
1997,
Pubmed
,
Xenbase
Savchenko,
Cyclic-nucleotide-gated channels mediate synaptic feedback by nitric oxide.
,
Pubmed
Serre,
Effects of cysteine modification on the activity of the cGMP-gated channel from retinal rods.
1995,
Pubmed
Stryer,
Visual excitation and recovery.
1991,
Pubmed
Stühmer,
Electrophysiological recording from Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Sun,
Exposure of residues in the cyclic nucleotide-gated channel pore: P region structure and function in gating.
1996,
Pubmed
Varnum,
Interdomain interactions underlying activation of cyclic nucleotide-gated channels.
1997,
Pubmed
,
Xenbase
Xu,
Identification of channel-lining residues in the M2 membrane-spanning segment of the GABA(A) receptor alpha1 subunit.
1996,
Pubmed
,
Xenbase
Yang,
Evidence for voltage-dependent S4 movement in sodium channels.
1995,
Pubmed
Yau,
Cyclic nucleotide-gated channels: an expanding new family of ion channels.
1994,
Pubmed
Zimmerman,
Cyclic GMP-sensitive conductance of retinal rods consists of aqueous pores.
,
Pubmed
Zimmerman,
Hindered diffusion in excised membrane patches from retinal rod outer segments.
1988,
Pubmed
Zimmerman,
Cyclic nucleotide gated channels.
1995,
Pubmed
Zong,
Three amino acids in the C-linker are major determinants of gating in cyclic nucleotide-gated channels.
1998,
Pubmed
Zufall,
Cyclic nucleotide gated channels as regulators of CNS development and plasticity.
1997,
Pubmed
