Gating small conductance calcium-activated potassium channels in the thalamic reticular nucleus.
SK channels
neurodevelopmental disorders
patch clamp
schizophrenia
thalamic reticular nucleus
Journal
Synapse (New York, N.Y.)
ISSN: 1098-2396
Titre abrégé: Synapse
Pays: United States
ID NLM: 8806914
Informations de publication
Date de publication:
14 Oct 2023
14 Oct 2023
Historique:
revised:
14
09
2023
received:
14
04
2023
accepted:
18
09
2023
medline:
15
10
2023
pubmed:
15
10
2023
entrez:
14
10
2023
Statut:
aheadofprint
Résumé
Small conductance calcium-activated potassium (SK) channels are well-known regulators of neuronal excitability. In the thalamic hub, SK2 channels act as pacemakers of thalamic reticular neurons, which play a key role in the thalamocortical circuit. Several disease-linked genes are highly enriched in these neurons, including genes known to be associated with schizophrenia and attentional disorders, which could affect neuronal firing. The present study assessed the effect of pharmacological modulation of SK channels in the firing pattern and intrinsic properties of thalamic reticular neurons by performing whole cell patch clamp recordings in brain slices. Two SK positive allosteric modulators and one negative allosteric modulator were used: CyPPA, NS309, and NS8593, respectively. By acting on the burst afterhyperpolarization (AHP), negative modulation of SK channels resulted in increased action potential (AP) firing, increased burst duration, and decreased intervals between bursts. Conversely, both CyPPA and NS309 increased the afterburst AHP, prolonging the interburst interval, which additionally resulted in reduced AP firing in the case of NS309. Alterations in SK channel activity would be expected to alter functioning of thalamocortical circuits. Targeting SK channels could be promising in treating disorders involving thalamic reticular dysfunction such as psychiatric and neurodevelopmental disorders.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Marie Sklodowska-Curie Actions (MSCA)
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : 813986
Informations de copyright
© 2023 The Authors. Synapse published byWiley Periodicals LLC.
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