Sodium leak channel NALCN

Definition

Voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability. NALCN channel functions as a multi-protein complex, which consists at least of NALCN, NALF1, UNC79 and UNC80. NALCN is the voltage-sensing, pore-forming subunit of the NALCN channel complex. NALCN channel complex is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations. In addition to its role in regulating neuronal excitability, is required for normal respiratory rhythm, systemic osmoregulation by controlling the serum sodium concentration and in the regulation of the intestinal pace-making activity in the interstitial cells of Cajal (By similarity). NALCN channel is also activated by neuropeptides such as neurotensin and substance P (SP) through a SRC family kinases-dependent pathway (By similarity). In addition, NALCN activity is enhanced/modulated by several GPCRs, such as CHRM3 (By similarity).

References:

[1]. Jiongfang Xie, et al. Structure of the human sodium leak channel NALCN in complex with FAM155A. Nat Commun. 2020 Nov 17;11(1):5831. [Content Brief]

[2]. H C Chua, et al. The NALCN channel complex is voltage sensitive and directly modulated by extracellular calcium. Sci Adv. 2020 Apr 24;6(17):eaaz3154. [Content Brief]

[3]. Boxun Lu, et al. The neuronal channel NALCN contributes resting sodium permeability and is required for normal respiratory rhythm. Cell. 2007 Apr 20;129(2):371-83. [Content Brief]

[4]. Malik Bouasse, et al. Functional expression of CLIFAHDD and IHPRF pathogenic variants of the NALCN channel in neuronal cells reveals both gain- and loss-of-function properties. Sci Rep. 2019 Aug 13;9(1):11791. [Content Brief]

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