Effectors of large-conductance calcium-activated potassium channel modulate glutamate excitotoxicity in organotypic hippocampal slice cultures


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Acta Neurobiologiae Experimentalis

Nencki Institute of Experimental Biology

Subject: Behavioral Sciences, Biomedical Sciences & Nutrition, Life Sciences, Medicine, Neurosciences


ISSN: 0065-1400
eISSN: 1689-0035





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VOLUME 76 , ISSUE 1 (March 2016) > List of articles

Effectors of large-conductance calcium-activated potassium channel modulate glutamate excitotoxicity
in organotypic hippocampal slice cultures

Marta Piwońska / Adam Szewczyk / Ulrich H. Schröder / Klaus G. Reymann / Piotr Bednarczyk *

Keywords : potassium channel, glutamate, hippocampal slice cultures, mitochondria, respiration, patch-clamp

Citation Information : Acta Neurobiologiae Experimentalis. Volume 76, Issue 1, Pages 20-31, DOI: https://doi.org/10.21307/ane-2017-002

License : (CC BY 4.0)

Received Date : 29-October-2015 / Accepted: 07-January-2016 / Published Online: 14-August-2017



Mitochondria have been suggested as a potential target for cytoprotective strategies. It has been shown that increased K+ uptake mediate by mitochondrial ATP-regulated potassium channels (mitoKATP channel) or large-conductance Ca2+-activated potassium channels (mitoBKCa channel) may provide protection in different models of cell death. Since recent findings demonstrated the presence of BKCa channels in neuronal mitochondria, the goal of the present study was to test the potential neuroprotective effects of BKCa channel modulators. Using organotypic hippocampal slice cultures exposed to glutamate, we demonstrated that preincubation of the slices with the BKCa channel opener NS1619 resulted in decreased neuronal cell death measured as reduced uptake of propidium iodide. This neuroprotective effect was reversed by preincubation with the BKCa channel inhibitors paxilline and Iberiotoxin (IbTx). Moreover, mitochondrial respiration
measurements revealed that NS1619 induced an IbTx-sensitive increase in state 2 respiration of isolated brain mitochondria. In addition,electrophysiological patch-clamp studies confirmed the presence of BKCa channels in mitoplasts isolated from embryonic hippocampal cells. Taken together, our results confirm presence of BKCa channel in rat hippocampal neurons mitochondria and suggest putative role for mitoBKCa in neuroprotection.

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