{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:03:00Z","timestamp":1770904980811,"version":"3.50.1"},"posted":{"date-parts":[[2024,6,2]]},"group-title":"Physiology","reference-count":34,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,6,2]],"date-time":"2024-06-02T00:00:00Z","timestamp":1717286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  At the end of pregnancy, the uterus transitions from a quiescent to a highly contractile state. This is partly due to depolarization of the resting membrane potential in uterine (myometrial) smooth muscle cells (MSMCs). In human MSMCs, the membrane potential is regulated by a functional complex between the sodium (Na\n                  <jats:sup>+<\/jats:sup>\n                  )-activated potassium (K\n                  <jats:sup>+<\/jats:sup>\n                  ) channel SLO2.1 and the Na\n                  <jats:sup>+<\/jats:sup>\n                  Leak Channel Non-Selective (NALCN). Na\n                  <jats:sup>+<\/jats:sup>\n                  entering through NALCN activates SLO2.1, leading to K\n                  <jats:sup>+<\/jats:sup>\n                  efflux, membrane hyperpolarization (cells become more negative inside), and reduced contractility. Decreased SLO2.1\/NALCN activity results in reduced K\n                  <jats:sup>+<\/jats:sup>\n                  efflux, leading to membrane depolarization, Ca\n                  <jats:sup>2+<\/jats:sup>\n                  influx via voltage-dependent calcium channels, and increased MSMC contractility. However, all of these data are from MSMCs isolated from women at term, so the role of the SLO2.1\/NALCN complex early in pregnancy was speculative. To address this question here, we examined the role of the SLO2.1\/NALCN complex in regulating mouse MSMC membrane potential across pregnancy. We report that\n                  <jats:italic>Slo2.1<\/jats:italic>\n                  and\n                  <jats:italic>Nalcn<\/jats:italic>\n                  are more highly expressed in MSMCs from non-pregnant and early pregnant mice than in those from late-pregnant mice. Functional studies revealed that SLO2.1 channels mediate a significant portion of the K\n                  <jats:sup>+<\/jats:sup>\n                  current in mouse MSMCs, particularly in cells from non-pregnant and early pregnant mice. Activation of SLO2.1 by Na\n                  <jats:sup>+<\/jats:sup>\n                  influx through NALCN led to membrane hyperpolarization in MSMCs from early pregnancy but not in MSMCs from later pregnancy. Moreover, the NALCN\/SLO2.1 complex regulates intracellular Ca\n                  <jats:sup>2+<\/jats:sup>\n                  responses more in MSMCs from non-pregnant and early pregnancy mice than in MSMCs from late pregnancy. Together, these findings reveal that the SLO2.1\/NALCN functional complex is conserved between mouse and humans and functions throughout pregnancy. This work could open avenues for targeted pharmacological interventions for pregnancy-related complications.\n                <\/jats:p>","DOI":"10.1101\/2024.05.29.596465","type":"posted-content","created":{"date-parts":[[2024,6,2]],"date-time":"2024-06-02T19:40:22Z","timestamp":1717357222000},"source":"Crossref","is-referenced-by-count":2,"title":["SLO2.1\/NALCN Functional Complex Activity in Mouse Myometrial Smooth Muscle Cells During Pregnancy"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8175-9067","authenticated-orcid":false,"given":"Juan J.","family":"Ferreira","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsey N.","family":"Kent","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Butler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofeng","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikita","family":"Peramsetty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chinwendu","family":"Amazu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace C.","family":"Whitter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah K.","family":"England","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celia 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