Oleic Acid Could Act as a Channel Blocker in the Inhibition of nAChR: Insights from Molecular Dynamics Simulations.
J Phys Chem B
; 128(10): 2398-2411, 2024 Mar 14.
Article
in En
| MEDLINE
| ID: mdl-38445598
ABSTRACT
The activation of the muscular nicotinic acetylcholine receptor (nAChR) produces the opening of the channel, with the consequent increase in the permeability of cations, triggering an excitatory signal. Free fatty acids (FFA) are known to modulate the activity of the receptor as noncompetitive antagonists, acting at the membrane-AChR interface. We present molecular dynamics simulations of a model of nAChR in a desensitized closed state embedded in a lipid bilayer in which distinct membrane phospholipids were replaced by two different monounsaturated FFA that differ in the position of a double bond. This allowed us to detect and describe that the cis-181ω-9 FFA were located at the interface between the transmembrane segments of α2 and γ subunits diffused into the channel lumen with the consequent potential ability to block the channel to the passage of ions.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Nicotinic
Limits:
Animals
Language:
En
Journal:
J Phys Chem B
Journal subject:
QUIMICA
Year:
2024
Document type:
Article
Affiliation country:
Argentina