New insights into the physiology and pathophysiology of the atypical sodium leak channel NALCN, 2023, Arnaud Monteil et al

Abstract
Cell excitability and its modulation by hormones and neurotransmitters involve the concerted action of membrane proteins, especially ion channels. Unique complements of co-expressed ion channels are exquisitely balanced against each other in different excitable cell types, establishing distinct electrical properties that are tailored for diverse physiological contributions, and dysfunction of any component may induce a disease state.

A crucial parameter controlling cell excitability is the resting membrane potential (RMP) set by extra- and intra-cellular concentrations of ions, mainly Na+, K+, and Cl-, and their passive permeation across the cell membrane through leak ion channels. Indeed, dysregulation of RMP causes significant effects on cellular excitability.

This review describes the molecular and physiological properties of the Na+ leak channel NALCN, which associates with its accessory subunits UNC-79, UNC-80, and NLF-1/FAM155 to conduct depolarizing background Na+ currents in various excitable cell types, especially neurons.

Studies of animal models clearly demonstrate that NALCN contributes to fundamental physiological processes in the nervous system including the control of respiratory rhythm, circadian rhythm, sleep and locomotor behavior. Furthermore, dysfunction of NALCN and its subunits is associated with severe pathological states in humans. The critical involvement of NALCN in physiology is now well established, but its study has been hampered by the lack of specific drugs that can block or agonize NALCN currents in vitro and in vivo. Molecular tools and animal models are now available to accelerate our understanding of how NALCN contributes to key physiological functions, and the development of novel therapies for NALCN channelopathies.

https://journals.physiology.org/doi/abs/10.1152/physrev.00014.2022

 

It's like trying to share the gravity of ME/CFS to not just healthy people, but to other chronically ill - you have to live with a channelopathy, or live with someone who has one, to grok it.

 

How do you find out if you have one?

 

There are some genetic tests. Not many.

There are a handful of neurologists that might make a clinical call.

Sorry, I don't remember in general how testing is done. I know only one rare type, and it's a genetic one. I think testing sodium/potassium/calcium levels while episodic might be a way?

If you're interested to learn more, check out https://periodicparalysis.org/

It's called, in some circles, periodic paralysis, but for most it's profound muscle weakness along with a constellation of other symptoms. Similar in some regards to ME/CFS.

 

Oh thanks @duncan, that’s been on my list to try to understand for while, due how it always floats around discussions of muscle weakness.