Evidence map›Paper›PMID 16157588›Full record

ArticleThe Journal of biological chemistry2005

Structural determinants of L-type channel activation in segment IIS6 revealed by a retinal disorder.

Annette Hohaus, Stanislav Beyl, Michaela Kudrnac, Stanislav Berjukow, Eugen N Timin, Rainer Marksteiner, Marion A Maw, Steffen Hering

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed.

  1. Identification of novel functional sites in the CaProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Inactivation of CaV1 and CaV2 channels.The Journal of general physiology · 2025
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. De novo CACNA1D CaPflugers Archiv : European journal of physiology · 2020
    Review
  10. Article
  11. Article
  12. β-Subunit of the voltage-gated CaProceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  13. Calcium channel gating.Pflugers Archiv : European journal of physiology · 2018
    Review
  14. Article
  15. Article
  16. Upward movement of IS4 and IIIS4 is a rate-limiting stage in CaPflugers Archiv : European journal of physiology · 2016
    Article
  17. Article
  18. Article
  19. Article
  20. Methods for quantification of pore-voltage sensor interaction in Ca(V)1.2.Pflugers Archiv : European journal of physiology · 2014
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Annette HohausInstitute for Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, A-1090 Wien.
Stanislav Beyl
Michaela Kudrnac
Stanislav Berjukow
Eugen N Timin
Rainer Marksteiner
Marion A Maw
Steffen Hering

Funding

Austrian Science Fund FWF P 15914
6 · The paper itself

Abstract

The mechanism of channel opening for voltage-gated calcium channels is poorly understood. The importance of a conserved isoleucine residue in the pore-lining segment IIS6 has recently been highlighted by functional analyses of a mutation (I745T) in the Ca(V)1.4 channel causing severe visual impairment (Hemara-Wahanui, A., Berjukow, S., Hope, C. I., Dearden, P. K., Wu, S. B., Wilson-Wheeler, J., Sharp, D. M., Lundon-Treweek, P., Clover, G. M., Hoda, J. C., Striessnig, J., Marksteiner, R., Hering, S., and Maw, M. A. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 7553-7558). In the present study we analyzed the influence of amino acids in segment IIS6 on gating of the Ca(V)1.2 channel. Substitution of Ile-781, the Ca(V)1.2 residue corresponding to Ile-745 in Ca(V)1.4, by residues of different hydrophobicity, size and polarity shifted channel activation in the hyperpolarizing direction (I781P > I781T > I781N > I781A > I781L). As I781P caused the most dramatic shift (-37 mV), substitution with this amino acid was used to probe the role of other residues in IIS6 in the process of channel activation. Mutations revealed a high correlation between the midpoint voltages of activation and inactivation. A unique kinetic phenotype was observed for residues 779-782 (LAIA) located in the lower third of segment IIS6; a shift in the voltage dependence of activation was accompanied by a deceleration of activation at hyperpolarized potentials, a deceleration of deactivation at all potentials (I781P and I781T), and decreased inactivation. These findings indicate that Ile-781 substitutions both destabilize the closed conformation and stabilize the open conformation of Ca(V)1.2. Moreover there may be a flexible center of helix bending at positions 779-782 of Ca(V)1.2. These four residues are completely conserved in high voltage-activated calcium channels suggesting that these channels may share a common mechanism of gating.

Indexed as

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl esterAmino Acid SequenceArginineBariumCalciumCalcium Channels, L-TypeCell LineGreen Fluorescent ProteinsHumansIonsIsoleucineKineticsMembrane PotentialsMicroscopy, ConfocalMolecular Sequence DataMutagenesis, Site-Directed3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl esterArginineBariumCalciumCalcium Channels, L-TypeGreen Fluorescent ProteinsIonsIsoleucineL-type calcium channel alpha(1C)

Identifiers

PMID16157588
PMCPMC3189691

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Registered trials

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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.