Evidence map›Paper›PMID 40175736›Full record

ReviewNature reviews. Neuroscience2025

Sculpting excitable membranes: voltage-gated ion channel delivery and distribution.

Sidharth Tyagi, Grant P Higerd-Rusli, Elizabeth J Akin, Stephen G Waxman, Sulayman D Dib-Hajj

Abstract readReview
In one paragraph

Review in Nature reviews. Neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Review
  2. Article
  3. Antigen-Detected NMR for Minimal Epitope Engineering and Structure-Guided Selection of a NaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Biomolecules · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Enhanced trafficking of an inherited erythromelalgia NaNeurobiology of pain (Cambridge, Mass.)
    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

5 authors.

Sidharth TyagiDepartment of Neurology, Yale School of Medicine, New Haven, CT, USA. sidharth.tyagi@yale.edu.ORCID http://orcid.org/0000-0001-6097-0541
Grant P Higerd-RusliDepartment of Neurology, Yale School of Medicine, New Haven, CT, USA.
Elizabeth J AkinDepartment of Neurology, Yale School of Medicine, New Haven, CT, USA.
Stephen G WaxmanDepartment of Neurology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-5718-7177
Sulayman D Dib-HajjDepartment of Neurology, Yale School of Medicine, New Haven, CT, USA. sulayman.dib-hajj@yale.edu.ORCID http://orcid.org/0000-0002-4137-1655

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Molecular mechanisms of sympatho-excitation in cardiovascular diseaseR01HL174439 · NHLBI · UNIVERSITY OF NEVADA RENO · PI Elizabeth Akin · 2024 to 2026
$1.4M
Mechanisms and specificity of sodium channel trafficking: Developing a novel analgesic strategyF31NS122417 · NINDS · YALE UNIVERSITY · PI HIGERD, GRANT PHILIP · 2021 to 2022
$62k
Targeted degradation of NaV1.8 as a therapeutic strategy for painF31NS135909 · NINDS · YALE UNIVERSITY · PI TYAGI, SIDHARTH · 2024 to 2024
$32k
BLRD VA I01 BX004899NHLBI NIH HHS R01 HL174439NIGMS NIH HHS T32 GM007205NINDS NIH HHS F31 NS122417NINDS NIH HHS F31 NS135909RRD VA I01 RX003621
6 · The paper itself

Abstract

The polarized and domain-specific distribution of membrane ion channels is essential for neuronal homeostasis, but delivery of these proteins to distal neuronal compartments (such as the axonal ends of peripheral sensory neurons) presents a logistical challenge. Recent developments have enabled the real-time imaging of single protein trafficking and the investigation of the life cycle of ion channels across neuronal compartments. These studies have revealed a highly regulated process involving post-translational modifications, vesicular sorting, motor protein-driven transport and targeted membrane insertion. Emerging evidence suggests that neuronal activity and disease states can dynamically modulate ion channel localization, directly influencing excitability. This Review synthesizes current knowledge on the spatiotemporal regulation of ion channel trafficking in both central and peripheral nervous system neurons. Understanding these processes not only advances our fundamental knowledge of neuronal excitability, but also reveals potential therapeutic targets for disorders involving aberrant ion channel distribution, such as chronic pain and neurodegenerative diseases.

Indexed as

Cell MembraneIon Channel GatingIon ChannelsNeuronsAnimalsHumansProtein TransportIon Channels

Identifiers

PMID40175736
PMCPMC12828907

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.