Evidence map›Paper›PMID 23129643›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Functional and structural analysis of the human SLO3 pH- and voltage-gated K+ channel.

Manuel D Leonetti, Peng Yuan, Yichun Hsiung, Roderick Mackinnon

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
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

40 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
  2. Article
  3. Andrology · 2025
    Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. SLO3: A Conserved Regulator of Sperm Membrane Potential.International journal of molecular sciences · 2023
    Review
  9. Pharmacological Evidence Suggests That Slo3 Channel Is the Principal KInternational journal of molecular sciences · 2023
    Article
  10. Review
  11. SLO3 in the fast lane: The latest male contraceptive target with a promising small-molecule inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. A selective inhibitor of the sperm-specific potassium channel SLO3 impairs human sperm function.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  13. Article
  14. Article
  15. Review
  16. Calcium-Activated KHandbook of experimental pharmacology · 2021
    Article
  17. Article
  18. Article
  19. Cloning and characterization of the rat Slo3 (KBritish journal of pharmacology · 2020
    Article
  20. Review
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

4 authors at 2 institutions in 1 country.

Manuel D LeonettiLaboratory of Molecular Neurobiology and Biophysics and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Peng Yuan
Yichun Hsiung
Roderick Mackinnon
Howard Hughes Medical Institute · USRockefeller University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The activation of eukaryotic SLO K(+) channels by intracellular cues, mediated by a cytoplasmic structure called the gating ring, is central to their physiological roles. SLO3 channels are exclusively expressed in mammalian sperm, where variations of intracellular pH are critical to cellular function. Previous studies primarily focused on the mouse SLO3 orthologue and revealed that, in murine sperm, SLO3 mediates a voltage- and alkalization-activated K(+) current essential to male fertility. Here we investigate the activation of the human SLO3 channel by intracellular pH at the functional and structural level. By using electrophysiology in a heterologous system, we show that human SLO3 opens upon intracellular pH increase and that its expression and functional properties are modulated by LRRC52, a testis-specific accessory subunit. We next present the crystal structure of the human SLO3 gating ring. Comparison with the known structures of the corresponding domain from SLO1, a Ca(2+)-activated homologue, suggests that the SLO3 gating ring structure may represent an open state. Together, these results present insights into the function of a protein expected to be critical for human reproduction and provide a framework to study the mechanism of pH gating in SLO3 channels.

Indexed as

Ion Channel GatingAnimalsHumansHydrogen-Ion ConcentrationLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsLarge-Conductance Calcium-Activated Potassium ChannelsMembrane ProteinsMiceModels, MolecularOocytesPotassium Channels, Voltage-GatedProtein ConformationProtein SubunitsStructural Homology, ProteinXenopusKCNMA1 protein, humanKCNU1 protein, humanLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsLarge-Conductance Calcium-Activated Potassium ChannelsLRRC52 protein, humanMembrane ProteinsPotassium Channels, Voltage-GatedProtein Subunits

Identifiers

PMID23129643
PMCPMC3511096
OpenAlexW2115766532

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.