Evidence map›Paper›PMID 37280215›Full record

ArticleNature communications2023

Native American ataxia medicines rescue ataxia-linked mutant potassium channel activity via binding to the voltage sensing domain.

Rían W Manville, J Alfredo Freites, Richard Sidlow, Douglas J Tobias, Geoffrey W Abbott

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

8 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. A conifer metabolite corrects episodic ataxia type 1 by voltage sensor-mediated ligand activation of Kv1.1.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
  6. Polymodal KCommunications biology · 2024
    Article
  7. International journal of molecular sciences · 2024
    Review
  8. 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

5 authors at 2 institutions in 1 country.

Rían W ManvilleBioelectricity Laboratory, Dept. of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, USA.
J Alfredo FreitesDepartment of Chemistry, University of California, Irvine, CA, USA.ORCID 0000-0001-5842-7443
Richard SidlowValley Children's Hospital, Madera, CA, USA.
Douglas J TobiasDepartment of Chemistry, University of California, Irvine, CA, USA.
Geoffrey W AbbottBioelectricity Laboratory, Dept. of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, USA. abbottg@hs.uci.edu.ORCID 0000-0003-4552-496X
University of California, Irvine · USChildren's Hospital Central California · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

There are currently no drugs known to rescue the function of Kv1.1 voltage-gated potassium channels carrying loss-of-function sequence variants underlying the inherited movement disorder, Episodic Ataxia 1 (EA1). The Kwakwaka'wakw First Nations of the Pacific Northwest Coast used Fucus gardneri (bladderwrack kelp), Physocarpus capitatus (Pacific ninebark) and Urtica dioica (common nettle) to treat locomotor ataxia. Here, we show that extracts of these plants enhance wild-type Kv1.1 current, especially at subthreshold potentials. Screening of their constituents revealed that gallic acid and tannic acid similarly augment wild-type Kv1.1 current, with submicromolar potency. Crucially, the extracts and their constituents also enhance activity of Kv1.1 channels containing EA1-linked sequence variants. Molecular dynamics simulations reveal that gallic acid augments Kv1.1 activity via a small-molecule binding site in the extracellular S1-S2 linker. Thus, traditional Native American ataxia treatments utilize a molecular mechanistic foundation that can inform small-molecule approaches to therapeutically correcting EA1 and potentially other Kv1.1-linked channelopathies.

Indexed as

AtaxiaKv1.1 Potassium ChannelHumansIndigenous CanadiansIon Channel GatingMedicine, TraditionalMutationKv1.1 Potassium Channel

Identifiers

PMID37280215
PMCPMC10244465
OpenAlexW4379537449

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.