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

ABSTRACT: Summary 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. Graphical abstract Highlights • The SLO2.1/NALCN complex controls uterine excitability.• A decrease in SLO2.1/NALCN activity triggers uterine contractility. Biological sciences; Cellular physiology; Cell biology; Functional aspects of cell biology

SUBMITTER: Ferreira J

PROVIDER: S-EPMC8551532 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Genetic variants in components of the NALCN-UNC80-UNC79 ion channel complex cause a broad clinical phenotype (NALCN channelopathies).

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