The sodium leak channel NALCN regulates cell excitability of pituitary endocrine cells

Anterior pituitary endocrine cells that release hormones such as growth hormone and prolactin are excitable and fire action potentials. In these cells, several studies previously showed that extracellular sodium (Na⁺ ) removal resulted in a negative shift of the resting membrane potential (RMP) and a subsequent inhibition of the spontaneous firing of action potentials, suggesting the contribution of a Na⁺ background conductance. Here, we show that the Na⁺ leak channel NALCN conducts a Ca²⁺ - Gd³⁺ -sensitive and TTX-resistant Na⁺ background conductance in the GH₃ cell line, a cell model of pituitary endocrine cells. NALCN knockdown hyperpolarized the RMP, altered GH₃ cell electrical properties and inhibited prolactin secretion. Conversely, the overexpression of NALCN depolarized the RMP, also reshaping the electrical properties of GH₃ cells. Overall, our results indicate that NALCN is functional in GH₃ cells and involved in endocrine cell excitability as well as in hormone secretion. Indeed, the GH₃ cell line suitably models native pituitary cells that display a similar Na⁺ background conductance and appears as a proper cellular model to study the role of NALCN in cellular excitability.