ArticleThe Journal of biological chemistry2010
Structural determinants of the high affinity extracellular zinc binding site on Cav3.2 T-type calcium channels.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- T-type calcium channel modulation by hydrogen sulfide in neuropathic pain conditions.Frontiers in pharmacology · 2023Review
- Whole Exome Sequencing Identifies a Heterozygous Variant in the Cav1.3 GeneInternational journal of molecular sciences · 2022Article
- Targeting T-type/CaV3.2 channels for chronic pain.Translational research : the journal of laboratory and clinical medicine · 2021Review
- Loss of Znt8 function in diabetes mellitus: risk or benefit?Molecular and cellular biochemistry · 2021Review
- CaChannels (Austin, Tex.) · 2020Review
- Neuronal Cav3 channelopathies: recent progress and perspectives.Pflugers Archiv : European journal of physiology · 2020Review
- Submicromolar copper (II) ions stimulate transretinal signaling in the isolated retina from wild type but not from CaBMC ophthalmology · 2020Article
- Delineating an extracellular redox-sensitive module in T-type CaThe Journal of biological chemistry · 2020Article
- Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus.Medicines (Basel, Switzerland) · 2019Article
- Evolutionary insights into T-type CaThe Journal of general physiology · 2017Article
- Redox-Dependent Modulation of T-Type Ca(2+) Channels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P.Antioxidants & redox signaling · 2016Article
- Regulation of the T-type Ca(2+) channel Cav3.2 by hydrogen sulfide: emerging controversies concerning the role of H2 S in nociception.The Journal of physiology · 2016Review
- Genetic alteration of the metal/redox modulation of Cav3.2 T-type calcium channel reveals its role in neuronal excitability.The Journal of physiology · 2016Article
- Redox and trace metal regulation of ion channels in the pain pathway.The Biochemical journal · 2015Review
- Redox regulation of neuronal voltage-gated calcium channels.Antioxidants & redox signaling · 2014Review
- Models of calcium permeation through T-type channels.Pflugers Archiv : European journal of physiology · 2014Review
- Ins and outs of T-channel structure function.Pflugers Archiv : European journal of physiology · 2014Review
- Complex modulation of Ca(v)3.1 T-type calcium channel by nickel.Cellular and molecular life sciences : CMLS · 2013Article
- Zinc induces long-term upregulation of T-type calcium current in hippocampal neurons in vivo.The Journal of physiology · 2012Article
- Molecular and biophysical basis of glutamate and trace metal modulation of voltage-gated Ca(v)2.3 calcium channels.The Journal of general physiology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ca(v)3.2 T-type channels contain a high affinity metal binding site for trace metals such as copper and zinc. This site is occupied at physiologically relevant concentrations of these metals, leading to decreased channel activity and pain transmission. A histidine at position 191 was recently identified as a critical determinant for both trace metal block of Ca(v)3.2 and modulation by redox agents. His(191) is found on the extracellular face of the Ca(v)3.2 channel on the IS3-S4 linker and is not conserved in other Ca(v)3 channels. Mutation of the corresponding residue in Ca(v)3.1 to histidine, Gln(172), significantly enhances trace metal inhibition, but not to the level observed in wild-type Ca(v)3.2, implying that other residues also contribute to the metal binding site. The goal of the present study is to identify these other residues using a series of chimeric channels. The key findings of the study are that the metal binding site is composed of a Asp-Gly-His motif in IS3-S4 and a second aspartate residue in IS2. These results suggest that metal binding stabilizes the closed conformation of the voltage-sensor paddle in repeat I, and thereby inhibits channel opening. These studies provide insight into the structure of T-type channels, and identify an extracellular motif that could be targeted for drug development.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.