Journal Article

FZJ-2025-01881

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png BK channels mediate a presynaptic form of mGluR-LTD in the neonatal hippocampus

Ancatén-González, C. ; Meza, R. C. ; Gonzalez-Sanabria, N. ; Segura, I.FZJ* ; Alcaino, A. ; Peña-Pichicoi, A. ; Latorre, R. ; Chiu, C. Q. ; Chávez, A. E. (Corresponding author)

2025
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.2411506122  doi:10.34734/FZJ-2025-01881

Abstract: BK channels can control neuronal function, but their functional relevance in activity-dependent changes of synaptic function remains elusive. Here, we report that repetitive low-frequency stimulation activates BK channels through 12(S)HPETE, an arachidonic acid metabolite, produced downstream of postsynaptic metabotropic glutamate receptors (mGluRs) to trigger long-term depression (LTD) at CA3-CA1 synapses in hippocampal slices from P7-P10 mice. Activation of BK channels is subunit specific, as paxilline but not iberiotoxin blocked mGluR-LTD. Also, 12(S)HPETE does not change the electrophysiological properties of the BK channel when the BKα subunit is expressed alone but increases the channel open probability when the BKα is coexpressed with the β4-subunit. Our findings reveal an interaction between 12(S)HPETE and BK channels to regulate synaptic strength at central synapses and increase our understanding of the mechanisms underlying mGluR-LTD in the neonatal hippocampus that likely contribute to circuit maturation necessary for learning.

Note: This work was supported by the Chilean government through FONDECYT Regular #1201848 (A.E.C.), #1230265 (R.L.), #1171840 (C.Q.C.), ANID Millennium Science Initiative Program (P09-022F to R.L, C.Q.C., and A.E.C.), and the National Institute Award RO1GM030376 (R.L.). C.A.-G. and A.A. were supported by PhD fellowship from ANID #21201603 (C.A.-G.) and #21202136 (A.A.). R.C.M. was supported by ANID-FONDECYT postdoctorado Grant #3190793.

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Contributing Institute(s):

1. Molekular- und Zellphysiologie (IBI-1)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2025; 2025

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