@article{c67210aa56d948aca232e9af8d00b187,
title = "SLO2.1/NALCN a sodium signaling complex that regulates uterine activity",
abstract = "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 Ca2+ entry through voltage-dependent Ca2+ 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.",
keywords = "Biological sciences, Cell biology, Cellular physiology, Functional aspects of cell biology",
author = "Ferreira, {Juan J.} and Chinwendu Amazu and Puga-Molina, {Lis C.} and Xiaofeng Ma and England, {Sarah K.} and Santi, {Celia M.}",
note = "Funding Information: We thank Dr. Deborah Frank for critical review of the manuscript and Anthony Bartley and Chrystie Tyler for designing figures and providing graphical assistance. We also thank the clinical research nurses in the Department of Obstetrics and Gynecology at Barnes-Jewish Hospital for obtaining patients' consent and acquiring human myometrial biopsies. We thank the Washington University Flow Cytometry & Fluorescence-Activated Cell Sorting Cores for use of their FACS Canto II TM cytometer and guidance. This work was supported by NIH grant 1F30HD095591 (to C.A.), an American Physiological Society William Town send Porter Pre-doctoral Fellowship Award (to C.A.), March of Dimes grant #6-FY18-664 (to S.K.E.), National Institutes of Health grant R01HD088097 (to C.M.S. and S.K.E.), and the Department of Obstetrics and Gynecology at Washington University in St. Louis. Funding Information: We thank Dr. Deborah Frank for critical review of the manuscript and Anthony Bartley and Chrystie Tyler for designing figures and providing graphical assistance. We also thank the clinical research nurses in the Department of Obstetrics and Gynecology at Barnes-Jewish Hospital for obtaining patients' consent and acquiring human myometrial biopsies. We thank the Washington University Flow Cytometry & Fluorescence-Activated Cell Sorting Cores for use of their FACS Canto II TM cytometer and guidance. This work was supported by NIH grant 1F30HD095591 (to C.A.), an American Physiological Society William Town send Porter Pre-doctoral Fellowship Award (to C.A.), March of Dimes grant #6-FY18-664 (to S.K.E.), National Institutes of Health grant R01HD088097 (to C.M.S. and S.K.E.), and the Department of Obstetrics and Gynecology at Washington University in St. Louis. J.J.F. and C.A. designed, performed, and analyzed the experiments. L.C.P.M. assisted with the flow cytometry experiments. X.M. performed experiments. J.J.F. C.A. S.K.E. and C.M.S. analyzed data and interpreted the results. J.J.F. and C.A. prepared figures. J.J.F. C.A. S.K.E. and C.M.S. drafted the manuscript. J.J.F. C.A. L.C.P.M. X.M. S.K.E. and C.M.S. edited, revised, and approved the final version of the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = nov,
day = "19",
doi = "10.1016/j.isci.2021.103210",
language = "English",
volume = "24",
journal = "iScience",
issn = "2589-0042",
number = "11",
}