The sodium leak channel NALCN is a highly conserved crucial player of cell excitability

Electrical activity of excitable cells, such as neurons and endocrine cells, involves a coordinated and tightly regulated action of a panel of specialized proteins including ion channels, transporters, exchangers, and receptors for hormones and neurotransmitters (Kandel, 2013; Hille, 2001). Any alteration in the function of one component of this “Excitosome” induces a pathological state that may be not only severe, but also lethal in human. The sodium (Na+)-leak channel NALCN was isolated in 1999 (Lee et al, 1999) and later studies revealed that it conducts a background sodium influx and critically regulates the electrical activity of neurons (reviewed in Cochet-Bissuel et al, 2014). Indeed, disruption of NALCN expression in different types of neurons from several species led to a 15mV hyperpolarization of the resting membrane potential and a decrease of their firing rate (Lu et al, 2007, Lu et al, 2011; Xie et al, 2013; Gao et al, 2015; Flourakis et al, 2015; Lutas et al, 2016; Shi et al, 2016; Yeh et al, 2017; Ford et al, 2018). NALCN is mainly expressed in brain, spinal cord, heart and endocrine glands but also in the uterus and intestine. As a whole, functional studies revealed that NALCN is a crucial player of cell excitability and is involved in several fundamental physiological processes such as respiratory rhythm, circadian rhythm, locomotor behavior, pain sensitivity, sleep, gastrointestinal motility, systemic osmoregulation and parturition (reviewed in Cochet-Bissuel et al, 2014).
NALCN is involved in rare and severe genetic diseases
