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dc.contributor.author
Mukhtasimova, Nuriya
dc.contributor.author
Bouzat, Cecilia Beatriz
dc.contributor.author
Sine, Steve M.
dc.date.available
2024-09-23T13:57:37Z
dc.date.issued
2024-08-07
dc.identifier.citation
Mukhtasimova, Nuriya; Bouzat, Cecilia Beatriz; Sine, Steve M.; Novel interplay between agonist and calcium binding sites modulates drug potentiation of α7 acetylcholine receptor; Springer Nature; Cellular And Molecular Life Sciences; 81; 332; 7-8-2024; 1-17
dc.identifier.issn
1420-682X
dc.identifier.uri
http://hdl.handle.net/11336/244819
dc.description.abstract
Drug modulation of the α7 acetylcholine receptor has emerged as a therapeutic strategy for neurological, neurodegenerative, and infammatory disorders. α7 is a homo-pentamer containing topographically distinct sites for agonists, calcium, and drug modulators with each type of site present in fve 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 of potentiated openings. In receptors harboring fve agonist binding sites, PNU potentiates regardless of the presence or absence of calcium, whereas in receptors harboring one agonist binding site, PNU potentiates in the presence but not the absence of calcium. By varying the numbers of agonist and calcium binding sites we show that PNU potentiation of α7 depends on a balance between agonist occupancy of the orthosteric sites and calcium occupancy of the allosteric sites. The fndings suggest that in the local cellular environment, fuctuations in the concentrations of neurotransmitter and calcium may alter this balance and modulate the ability of PNU to potentiate α7
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer Nature
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
NICOTINIC RECEPTOR
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POSITIVE ALLOSTERIC MODULATOR
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SINGLE ION CHANNEL RECORDING
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PATCH CLAMP
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LIGAND-GATED ION CHANNEL
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Biofísica
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Novel interplay between agonist and calcium binding sites modulates drug potentiation of α7 acetylcholine receptor
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-09-09T13:34:48Z
dc.identifier.eissn
1420-9071
dc.journal.volume
81
dc.journal.number
332
dc.journal.pagination
1-17
dc.journal.pais
Suiza
dc.journal.ciudad
Cham
dc.description.fil
Fil: Mukhtasimova, Nuriya. Mayo Clinic College of Medicine and Science; Estados Unidos
dc.description.fil
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
dc.description.fil
Fil: Sine, Steve M.. Mayo Clinic College of Medicine and Science; Estados Unidos
dc.journal.title
Cellular And Molecular Life Sciences
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s00018-024-05374-1
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00018-024-05374-1
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