Functional specification of CCK+ interneurons by alternative isoforms of Kv4.3 auxiliary subunits.
GABAergic neurons
hippocampus
ionic channels
membrane excitability
neuroscience
oscillations
rat
splicing isoforms
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
03 06 2020
03 06 2020
Historique:
received:
02
05
2020
accepted:
20
05
2020
entrez:
4
6
2020
pubmed:
4
6
2020
medline:
24
2
2021
Statut:
epublish
Résumé
CCK-expressing interneurons (CCK+INs) are crucial for controlling hippocampal activity. We found two firing phenotypes of CCK+INs in rat hippocampal CA3 area; either possessing a previously undetected membrane potential-dependent firing or regular firing phenotype, due to different low-voltage-activated potassium currents. These different excitability properties destine the two types for distinct functions, because the former is essentially silenced during realistic 8-15 Hz oscillations. By contrast, the general intrinsic excitability, morphology and gene-profiles of the two types were surprisingly similar. Even the expression of Kv4.3 channels were comparable, despite evidences showing that Kv4.3-mediated currents underlie the distinct firing properties. Instead, the firing phenotypes were correlated with the presence of distinct isoforms of Kv4 auxiliary subunits (KChIP1 vs. KChIP4e and DPP6S). Our results reveal the underlying mechanisms of two previously unknown types of CCK+INs and demonstrate that alternative splicing of few genes, which may be viewed as a minor change in the cells' whole transcriptome, can determine cell-type identity.
Identifiants
pubmed: 32490811
doi: 10.7554/eLife.58515
pii: 58515
pmc: PMC7269670
doi:
pii:
Substances chimiques
Protein Subunits
0
Shal Potassium Channels
0
Cholecystokinin
9011-97-6
Banques de données
GEO
['GSE133951']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust International Senior Research Fellowship
ID : 087497
Pays : International
Organisme : Hungarian National Brain Research Program
ID : KTIA_13_NAP-A-I/15
Pays : International
Organisme : European Research Council Consolidator Grant
ID : ERC-CoG 772452
Pays : International
Organisme : Swiss National Science Foundation
ID : CRETP3_166815
Pays : Switzerland
Organisme : Swiss National Science Foundation
ID : 31003A_170085
Pays : Switzerland
Organisme : European Research Council Advance Grant
ID : ERC-AdG 787157
Pays : International
Informations de copyright
© 2020, Oláh et al.
Déclaration de conflit d'intérêts
VO, DL, JW, AA, AL, ZN, CF, JS No competing interests declared
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