Gating small conductance calcium-activated potassium channels in the thalamic reticular nucleus
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Gating small conductance calcium-activated potassium channels in the thalamic reticular nucleus. / Silván, Ágata; Kohlmeier, Kristi Anne; Herrik, Kjartan Frisch; Hougaard, Charlotte.
In: Synapse (New York, N.Y.), Vol. 78, No. 1, e22283, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Gating small conductance calcium-activated potassium channels in the thalamic reticular nucleus
AU - Silván, Ágata
AU - Kohlmeier, Kristi Anne
AU - Herrik, Kjartan Frisch
AU - Hougaard, Charlotte
N1 - © 2023 The Authors. Synapse published byWiley Periodicals LLC.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
U2 - 10.1002/syn.22283
DO - 10.1002/syn.22283
M3 - Journal article
C2 - 37837643
VL - 78
JO - Synapse
JF - Synapse
SN - 0887-4476
IS - 1
M1 - e22283
ER -
ID: 369985754