Desensitization of nicotinic ACh receptors: shaping cholinergic signaling.
Nicotinic ACh receptors (nAChRs) can undergo desensitization, a reversible reduction in response during sustained agonist application. Although the mechanism of desensitization remains incompletely understood, recent investigations have elucidated new properties underlying desensitization, indicating that it might be important to control synaptic efficacy, responses to cholinergic agents, and certain nAChR-related disease states. Thus, studying how different nAChR subunits contribute to desensitization might help to explain variations in responsiveness to drugs, and might thus improve their therapeutic applications. Agonist-specific desensitization, desensitization arising from resting receptors, natural mutations dramatically altering desensitization, and the possibility that recovery from desensitization is an important process for modulating receptor function, together provide a new framework for considering desensitization as a target to shape cholinergic signaling.
Neurobiology Sector and INFM Unit, International School for Advanced Studies (SISSA), Via Beirut 4, 34014, Trieste, Italy.
Rashid
R
Giniatullin
Andrea
A
Nistri
Jerrel L
JL
Yakel
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D011978:Receptors, Nicotinic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D011978:Receptors, Nicotinic; D000109:Acetylcholine