BK channels mediate a presynaptic form of mGluR-LTD in the neonatal hippocampus

• 成果类型: Article
• 署名作者: Ancaten-Gonzalez, Carlos; Meza, Rodrigo C.; Gonzalez -Sanabria, Naileth; Segura, Ignacio; Alcano, Alejandro; Pena-Pichicoi, Antonio; Latorre, Ramon; Chiu, Chiayu Q.; Chavez, Andres E.
• 署名单位: Universidad de Valparaiso; Universidad de Valparaiso
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12972
• DOI: 10.1073/pnas.2411506122
• 发表日期: 2025-01-14
• 关键词: long-term depression; ca2+-activated k+ channels; arachidonic-acid; neurotransmitter release; synaptic-transmission; transmitter release; trpv1 channels; modulation; activation; 12-lipoxygenase

摘要

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 BK alpha subunit is expressed alone but increases the channel open probability when the BK alpha is coexpressed with the (34- 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.