Novel interplay between agonist and calcium binding sites modulates drug potentiation of α7 acetylcholine receptor.

ABSTRACT: Drug modulation of the α7 acetylcholine receptor has emerged as a therapeutic strategy for neurological, neurodegenerative, and inflammatory disorders. α7 is a homo-pentamer containing topographically distinct sites for agonists, calcium, and drug modulators with each type of site present in five copies. However, functional relationships between agonist, calcium, and drug modulator sites remain poorly understood. To investigate these relationships, we manipulated the number of agonist binding sites, and monitored potentiation of ACh-elicited single-channel currents through α7 receptors by PNU-120596 (PNU) both in the presence and absence of calcium. When ACh is present alone, it elicits brief, sub-millisecond channel openings, however when ACh is present with PNU it elicits long clusters o

SUBMITTER: Mukhtasimova N 

PROVIDER: S-EPMC11335256 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature