Persistent Na+ influx drives L-type channel resting Ca2+ entry in rat melanotrophs

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

“…28,44 Importantly, a Na + background conductance was described in several cell types of the anterior pituitary gland, including in the somatolactotroph GH 3 cell line. [6][7][8][9][10][11][12][13][14][15] An important finding of this study is that the excitability properties of GH 3 cells rely on the expression level of NALCN. We report that the overexpression of NALCN depolarized the RMP while its knockdown led to a more negative RMP of GH 3 cells.…”

“…Indeed, several studies also suggested that TRP channels could be involved in the Na + background conductance of anterior pituitary cells as well as GH 3 cells. 11,12,15 This hypothesis was based on detectable mRNA expression of some TRP channels in these cell types. However, no genetic manipulation was carried out with any TRP channel.…”

“…Indeed, a Na + background conductance was suggested to belong to a common core set of ionic currents between the different subtypes of anterior pituitary endocrine cells 1 . This current maintains a relatively depolarized resting membrane potential (RMP) as demonstrated by the membrane hyperpolarization when Na + is replaced by large organic monovalent cations such as N‐methyl‐D‐glucamine (NMDG) or Tris or choline 6‐15 . However, the molecular identity of this background inward Na + current remains to be determined.…”

“…These cells also express high and low tetrodotoxin (TTX)‐sensitive voltage‐gated Na + (Na v ) channels 2‐5 . In addition to these conductances, several studies also revealed the existence of a TTX‐resistant background inward current carried by Na + in primary corticotrophs, gonadotrophs, lactotrophs, melanotrophs, and somatotrophs as well as in immortalized pituitary cells 6‐15 . Indeed, a Na + background conductance was suggested to belong to a common core set of ionic currents between the different subtypes of anterior pituitary endocrine cells 1 .…”

The sodium leak channel NALCN encodes the major background sodium ion conductance in mouse anterior pituitary cells

“…Replacing extracellular Na + with large impermeable cations such as NMDG + immediately suppresses the cell’s ability to become depolarised. Instead, hyperpolarises the RMP, silences firing activity and abolishes the [Ca 2+ ] i transients (Simasko, 1994; Sankaranarayan & Simasko, 1996; Kwiecien and Hammond, 1998; Tsaneva-Atanasova et al, 2007; Kucka et al, 2010, 2012; Tomic et al, 2011; Liang et al, 2011; Zemkova et al, 2016; Kayano et al, 2019). This reflects the presence of constitutively-active inward-depolarising currents in pituitary cells that set the membrane potential close to the firing threshold.…”