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.
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.
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15 citing papers in PubMed, 24 citations in OpenAlex.
- Myometrial smooth muscle KATP channel activity is attenuated in a mouse model of diet-induced obesity during pregnancy†.Biology of reproduction · 2025Article
- SLO2.1/NALCN Functional Complex Activity in Mouse Myometrial Smooth Muscle Cells During Pregnancy.Journal of cellular physiology · 2025Article
- Adiponectin and Glucocorticoids Modulate Risk for Preterm Birth: The Healthy Start Study.The Journal of clinical endocrinology and metabolism · 2025Article
- Review
- Whole-exome sequencing reveals candidate high-risk susceptibility genes for endometriosis.Human genomics · 2023Article
- The Donnan-dominated resting state of skeletal muscle fibers contributes to resilience and longevity in dystrophic fibers.The Journal of general physiology · 2022Article
- Modeling and experimental approaches for elucidating multi-scale uterine smooth muscle electro- and mechano-physiology: A review.Frontiers in physiology · 2022Review
- Article
- Uterine contractions in rodent models and humans.Acta physiologica (Oxford, England) · 2021Review
- Volatile Anesthetics Activate a Leak Sodium Conductance in Retrotrapezoid Nucleus Neurons to Maintain Breathing during Anesthesia in Mice.Anesthesiology · 2020Article
- Microelectrode array analysis of mouse uterine smooth muscle electrical activity†.Biology of reproduction · 2020Article
- Progesterone and estrogen regulate NALCN expression in human myometrial smooth muscle cells.American journal of physiology. Endocrinology and metabolism · 2020Article
- Sodium channels and transporters in the myometrium.Current opinion in physiology · 2020Article
- Molecular Studies on Pregnancy with Mouse Models.Current opinion in physiology · 2020Article
- Sodium-activated potassium channels moderate excitability in vascular smooth muscle.The Journal of physiology · 2019Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
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.
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