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

2021 
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 NALCN/SLO2.1 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 arrangement of SLO2.1 and NALCN permits these channels to functionally regulate MSMC membrane potential and cell excitability and modulate uterine contractility.
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