The NALCN channel complex is voltage sensitive and directly modulated by extracellular calcium.

ABSTRACT: The sodium leak channel (NALCN) is essential for survival in mammals: NALCN mutations are life-threatening in humans and knockout is lethal in mice. However, the basic functional and pharmacological properties of NALCN have remained elusive. Here, we found that robust function of NALCN in heterologous systems requires co-expression of UNC79, UNC80, and FAM155A. The resulting NALCN channel complex is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations. Our data support the notion that NALCN is directly responsible for the increased excitability observed in a variety of neurons in reduced extracellular Ca²⁺. Despite the smaller number of voltage-sensing residues in NALCN, the constitutive activity i

SUBMITTER: Chua HC 

PROVIDER: S-EPMC7182417 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature