Journal
FASEB JOURNAL
Volume 35, Issue 5, Pages -Publisher
WILEY
DOI: 10.1096/fj.202000841RR
Keywords
background conductance; extracellular Ca2+; ion channels; resting membrane potential
Categories
Funding
- Fondation pour la Recherche Medicale (FRM) [DEQ20170336728]
- Laboratory of Excellence 'Ion Channel Science and Therapeutics'
- Association Francaise contre les Myopathies (AFM) [20151]
- Fondation Maladies Rares
- Naresuan University (NU)
- French Ministry for Foreign Affairs
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The study reveals the functional role of the Na+ leak channel NALCN in GH(3) cells, affecting the electrical properties and hormone secretion 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 GH(3) cell line, a cell model of pituitary endocrine cells. NALCN knockdown hyperpolarized the RMP, altered GH(3) cell electrical properties and inhibited prolactin secretion. Conversely, the overexpression of NALCN depolarized the RMP, also reshaping the electrical properties of GH(3) cells. Overall, our results indicate that NALCN is functional in GH(3) cells and involved in endocrine cell excitability as well as in hormone secretion. Indeed, the GH(3) 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.
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