Cargando…
SLO2.1/NALCN a sodium signaling complex that regulates uterine activity
Depolarization of the myometrial smooth muscle cell (MSMC) resting membrane potential is necessary for the uterus to transition from a quiescent state to a contractile state. The molecular mechanisms involved in this transition are not completely understood. Here, we report that a coupled system bet...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551532/ https://www.ncbi.nlm.nih.gov/pubmed/34746693 http://dx.doi.org/10.1016/j.isci.2021.103210 |
_version_ | 1784591178934517760 |
---|---|
author | Ferreira, Juan J. Amazu, Chinwendu Puga-Molina, Lis C. Ma, Xiaofeng England, Sarah K. Santi, Celia M. |
author_facet | Ferreira, Juan J. Amazu, Chinwendu Puga-Molina, Lis C. Ma, Xiaofeng England, Sarah K. Santi, Celia M. |
author_sort | Ferreira, Juan J. |
collection | PubMed |
description | Depolarization of the myometrial smooth muscle cell (MSMC) resting membrane potential is necessary for the uterus to transition from a quiescent state to a contractile state. The molecular mechanisms involved in this transition are not completely understood. Here, we report that a coupled system between the Na(+)-activated K(+) channel (SLO2.1) and the non-selective Na(+) leak channel (NALCN) determines the MSMC membrane potential. Our data indicate that Na(+) entering through NALCN acts as an intracellular signaling molecule that activates SLO2.1. Potassium efflux through SLO2.1 hyperpolarizes the membrane. A decrease in SLO2.1/NALCN activity induces membrane depolarization, triggering Ca(2+) entry through voltage-dependent Ca(2+) channels and promoting contraction. Consistent with functional coupling, our data show that NALCN and SLO2.1 are in close proximity in human MSMCs. We propose that these arrangements of SLO2.1 and NALCN permit these channels to functionally regulate MSMC membrane potential and cell excitability and modulate uterine contractility. |
format | Online Article Text |
id | pubmed-8551532 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-85515322021-11-04 SLO2.1/NALCN a sodium signaling complex that regulates uterine activity Ferreira, Juan J. Amazu, Chinwendu Puga-Molina, Lis C. Ma, Xiaofeng England, Sarah K. Santi, Celia M. iScience Article Depolarization of the myometrial smooth muscle cell (MSMC) resting membrane potential is necessary for the uterus to transition from a quiescent state to a contractile state. The molecular mechanisms involved in this transition are not completely understood. Here, we report that a coupled system between the Na(+)-activated K(+) channel (SLO2.1) and the non-selective Na(+) leak channel (NALCN) determines the MSMC membrane potential. Our data indicate that Na(+) entering through NALCN acts as an intracellular signaling molecule that activates SLO2.1. Potassium efflux through SLO2.1 hyperpolarizes the membrane. A decrease in SLO2.1/NALCN activity induces membrane depolarization, triggering Ca(2+) entry through voltage-dependent Ca(2+) channels and promoting contraction. Consistent with functional coupling, our data show that NALCN and SLO2.1 are in close proximity in human MSMCs. We propose that these arrangements of SLO2.1 and NALCN permit these channels to functionally regulate MSMC membrane potential and cell excitability and modulate uterine contractility. Elsevier 2021-10-02 /pmc/articles/PMC8551532/ /pubmed/34746693 http://dx.doi.org/10.1016/j.isci.2021.103210 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Ferreira, Juan J. Amazu, Chinwendu Puga-Molina, Lis C. Ma, Xiaofeng England, Sarah K. Santi, Celia M. SLO2.1/NALCN a sodium signaling complex that regulates uterine activity |
title | SLO2.1/NALCN a sodium signaling complex that regulates uterine activity |
title_full | SLO2.1/NALCN a sodium signaling complex that regulates uterine activity |
title_fullStr | SLO2.1/NALCN a sodium signaling complex that regulates uterine activity |
title_full_unstemmed | SLO2.1/NALCN a sodium signaling complex that regulates uterine activity |
title_short | SLO2.1/NALCN a sodium signaling complex that regulates uterine activity |
title_sort | slo2.1/nalcn a sodium signaling complex that regulates uterine activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551532/ https://www.ncbi.nlm.nih.gov/pubmed/34746693 http://dx.doi.org/10.1016/j.isci.2021.103210 |
work_keys_str_mv | AT ferreirajuanj slo21nalcnasodiumsignalingcomplexthatregulatesuterineactivity AT amazuchinwendu slo21nalcnasodiumsignalingcomplexthatregulatesuterineactivity AT pugamolinalisc slo21nalcnasodiumsignalingcomplexthatregulatesuterineactivity AT maxiaofeng slo21nalcnasodiumsignalingcomplexthatregulatesuterineactivity AT englandsarahk slo21nalcnasodiumsignalingcomplexthatregulatesuterineactivity AT santiceliam slo21nalcnasodiumsignalingcomplexthatregulatesuterineactivity |