The existence of resting K⁺ conductance has been known for some time. Only recently has the Nalcn (sodium leak channel non-selective protein) been found responsible for the resting Na⁺ conductance¹.

Nalcn is a member of the Na_V and Ca_V channel family which have four homologous repeats of six transmembrane domains. One structural difference is that Nalcn is less positively charged in the voltage sensing segment¹. The protein forms voltage-independent non-inactivating channel which is permeable to Na⁺, K⁺ and Ca²⁺ ions^1,2.

Evidence suggests that Nalcn is a non-redundant and thus essential channel since knock-out mice display disrupted respiratory rhythm and die within 24 hours of birth. In addition, isolated neurons from these mice have decreased excitability¹.

The channel is extensively expressed in the central nervous system¹, heart, pituitary and adrenal glands and pancreatic islet cells^2,3.

In pancreatic islets, Nalcn is activated by acetylcholine via its physical association with M3 muscarinic receptor, and potentiates insulin secretion induced by glucose uptake^2-4.