Evidence map›Paper›PMID 30021195›Full record

ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2018

Na+-Leak Channel, Non-Selective (NALCN) Regulates Myometrial Excitability and Facilitates Successful Parturition.

Erin L Reinl, Peinan Zhao, Wenjie Wu, Xiaofeng Ma, Chinwendu Amazu, Rachael Bok, K Joseph Hurt, Yong Wang, Sarah K England

Open access · goldAbstract read
In one paragraph

Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
4.0field-weighted citation impact, top 7% 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

15 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
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  3. Adiponectin and Glucocorticoids Modulate Risk for Preterm Birth: The Healthy Start Study.The Journal of clinical endocrinology and metabolism · 2025
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  7. Review
  8. Article
  9. Uterine contractions in rodent models and humans.Acta physiologica (Oxford, England) · 2021
    Review
  10. Article
  11. Article
  12. Progesterone and estrogen regulate NALCN expression in human myometrial smooth muscle cells.American journal of physiology. Endocrinology and metabolism · 2020
    Article
  13. Sodium channels and transporters in the myometrium.Current opinion in physiology · 2020
    Article
  14. Molecular Studies on Pregnancy with Mouse Models.Current opinion in physiology · 2020
    Article
  15. 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

9 authors at 2 institutions in 1 country.

Erin L ReinlDepartment of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, USA.
Peinan ZhaoDepartment of Obstetrics and Gynecology, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, USA.
Wenjie WuDepartment of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, USA.
Xiaofeng MaDepartment of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, USA.
Chinwendu AmazuDepartment of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, USA.
Rachael BokDepartment of Obstetrics & Gynecology, Divisions of Reproductive Sciences and Maternal Fetal Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
K Joseph HurtDepartment of Obstetrics & Gynecology, Divisions of Reproductive Sciences and Maternal Fetal Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
Yong WangDepartment of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, USA.
Sarah K EnglandDepartment of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, USA.
Washington University in St. Louis · USUniversity of Colorado Denver · US

Funding

A NOVEL MOLECULAR MECHANISM FOR STIMULATING UTERINE CONTRACTILITY BY OXYTOCINR01HD088097 · NICHD · WASHINGTON UNIVERSITY · PI Sarah K. England, Celia M Santi · 2016 to 2026
$4.1M
Quantification of Neuroinflammation inAlzheimer's Disease Using Diffusion BasisSpectrum ImagingR01AG054567 · NIA · WASHINGTON UNIVERSITY · PI BENZINGER, TAMMIE LEE SMITH, WANG, YONG · 2017 to 2021
$3.6M
SLO3 KO MOUSE: A TOOL TO REVEAL VOLTAGE-DEPENDENT PROCESSES IN SPERM FERTILITYR01HD069631 · NICHD · WASHINGTON UNIVERSITY · PI SANTI, CELIA M · 2011 to 2022
$3.3M
Identification and Regulation of the Myometrial Leak CurrentF31HD079148 · NICHD · WASHINGTON UNIVERSITY · PI REINL, ERIN · 2014 to 2016
$72k
NICHD NIH HHS F31 HD079148NICHD NIH HHS R01 HD069631NICHD NIH HHS R01 HD088097
6 · The paper itself

Abstract

BACKGROUND/

aimsUterine contractility is controlled by electrical signals generated by myometrial smooth muscle cells. Because aberrant electrical signaling may cause inefficient uterine contractions and poor reproductive outcomes, there is great interest in defining the ion channels that regulate uterine excitability. In human myometrium, the Na+ leak channel, non-selective (NALCN) contributes to a gadolinium-sensitive, Na+-dependent leak current. The aim of this study was to determine the role of NALCN in regulating uterine excitability and examine its involvement in parturition.

methodsWildtype C57BL/6J mice underwent timed-mating and NALCN uterine expression was measured at several time points across pregnancy including pregnancy days 7, 10, 14, 18 and 19. Sharp electrode current clamp was used to measure uterine excitability at these same time points. To determine NALCN's contribution to myometrial excitability and pregnancy outcomes, we created smooth-muscle-specific NALCN knockout mice by crossing NALCNfx/fx mice with myosin heavy chain Cre (MHCCreeGFP) mice. Parturition outcomes were assessed by observation via surveillance video recording cre control, flox control, smNALCN+/-, and smNALCN-/- mice. Myometrial excitability was compared between pregnancy day 19 flox controls and smNALCN-/- mice.

resultsWe found that in the mouse uterus, NALCN protein levels were high early in pregnancy, decreased in mid and late pregnancy, and then increased in labor and postpartum. Sharp electrode current clamp recordings of mouse longitudinal myometrial samples from pregnancy days 7, 10, 14, 18, and 19 revealed day-dependent increases in burst duration and interval and decreases in spike density. NALCN smooth muscle knockout mice had reduced myometrial excitability exemplified by shortened action potential bursts, and an increased rate of abnormal labor, including prolonged and dysfunctional labor.

conclusionsTogether, our findings demonstrate that the Na+ conducting channel NALCN contributes to the myometrial action potential waveform and is important for successful labor outcomes.

Indexed as

Action PotentialsAnimalsFemaleIon ChannelsMaleMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMuscle, SmoothMyometriumNerve Tissue ProteinsPatch-Clamp TechniquesPregnancyUterine ContractionUterusIon ChannelsMembrane ProteinsNALCN protein, mouseNerve Tissue ProteinsIon channelsMyometriumNALCNParturitionUterine excitability

Identifiers

PMID30021195
PMCPMC9639199
OpenAlexW2884253463

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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.