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dc.contributor.author
Tian, Jin Bin
dc.contributor.author
Yang, Jane
dc.contributor.author
Joslin, William C.
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Flockerzi, Veit
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Prescott, Steven A.
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Birnbaumer, Lutz
dc.contributor.author
Zhu, Michael X.
dc.date.available
2023-11-01T11:03:52Z
dc.date.issued
2022-05
dc.identifier.citation
Tian, Jin Bin; Yang, Jane; Joslin, William C.; Flockerzi, Veit; Prescott, Steven A.; et al.; TRPC4 and GIRK channels underlie neuronal coding of firing patterns that reflect Gq/11-Gi/o coincidence signals of variable strengths; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 119; 20; 5-2022; 1-10
dc.identifier.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/216722
dc.description.abstract
Transient receptor potential canonical 4 (TRPC4) is a receptor-operated cation channel codependent on both the Gq/11-phospholipase C signaling pathway and Gi/o proteins for activation. This makes TRPC4 an excellent coincidence sensor of neurotransmission through Gq/11- and Gi/o-coupled receptors. In whole-cell slice recordings of lateral septal neurons, TRPC4 mediates a strong depolarizing plateau that shuts down action potential firing, which may or may not be followed by a hyperpolarization that extends the firing pause to varying durations depending on the strength of Gi/o stimulation. We show that the depolarizing plateau is codependent on Gq/11-coupled group I metabotropic glutamate receptors and on Gi/o-coupled γ-aminobutyric acid type B receptors. The hyperpolarization is mediated by Gi/o activation of G protein-activated inwardly rectifying K+ (GIRK) channels. Moreover, the firing patterns, elicited by either electrical stimulation or receptor agonists, encode information about the relative strengths of Gq/11 and Gi/o inputs in the following fashion. Pure Gq/11 input produces weak depolarization accompanied by firing acceleration, whereas pure Gi/o input causes hyperpolarization that pauses firing. Although coincident Gq/11-Gi/o inputs also pause firing, the pause is preceded by a burst, and both the pause duration and firing recovery patterns reflect the relative strengths of Gq/11 versus Gi/o inputs. Computer simulations demonstrate that different combinations of TRPC4 and GIRK conductances are sufficient to produce the range of firing patterns observed experimentally. Thus, concurrent neurotransmission through the Gq/11 and Gi/o pathways is converted to discernible electrical responses by the joint actions of TRPC4 and GIRK for communication to downstream neurons.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
National Academy of Sciences
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
COINCIDENCE DETECTION
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G PROTEINS
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NEURONAL FIRING
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NEUROTRANSMISSION
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TRP CHANNELS
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Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
TRPC4 and GIRK channels underlie neuronal coding of firing patterns that reflect Gq/11-Gi/o coincidence signals of variable strengths
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-10-30T17:57:20Z
dc.journal.volume
119
dc.journal.number
20
dc.journal.pagination
1-10
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Tian, Jin Bin. University of Texas; Estados Unidos
dc.description.fil
Fil: Yang, Jane. University Of Toronto. Hospital For Sick Children; Canadá
dc.description.fil
Fil: Joslin, William C.. University of Texas; Estados Unidos
dc.description.fil
Fil: Flockerzi, Veit. Universitat Saarland; Alemania
dc.description.fil
Fil: Prescott, Steven A.. University Of Toronto. Hospital For Sick Children; Canadá
dc.description.fil
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
dc.description.fil
Fil: Zhu, Michael X.. University of Texas; Estados Unidos
dc.journal.title
Proceedings of the National Academy of Sciences of The United States of America
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073/pnas.2120870119
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