SLO2.1/NALCN a sodium signaling complex that regulates uterine activity

Juan J Ferreira; Chinwendu Amazu; Lis C Puga-Molina; Xiaofeng Ma; Sarah K England; Celia M Santi

doi:10.1016/j.isci.2021.103210

SLO2.1/NALCN a sodium signaling complex that regulates uterine activity

iScience. 2021 Oct 2;24(11):103210. doi: 10.1016/j.isci.2021.103210. eCollection 2021 Nov 19.

Authors

Juan J Ferreira^{1

2}, Chinwendu Amazu¹, Lis C Puga-Molina¹, Xiaofeng Ma¹, Sarah K England¹, Celia M Santi^{1

2}

Affiliations

¹ Department of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University in St. Louis, School of Medicine, 425 S. Euclid Avenue, CB 8064, St. Louis, MO 63110, USA.
² Department of Neuroscience, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.

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.

Abstract

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