BAD and K<sub>ATP</sub> channels regulate neuron excitability and epileptiform activity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29368690.
- Also identified by DOI 10.7554/eLife.32721 and PMC identifier 5785210.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Brain metabolism can profoundly influence neuronal excitability. Mice with genetic deletion or alteration of <i>Bad</i> (<u>B</u>CL-2 <u>a</u>gonist of cell <u>d</u>eath) exhibit altered brain-cell fuel metabolism, accompanied by resistance to acutely induced epileptic seizures; this seizure protection is mediated by ATP-sensitive potassium (K<sub>ATP</sub>) channels. Here we investigated the effect of BAD manipulation on K<sub>ATP</sub> channel activity and excitability in acute brain slices. We found that BAD's influence on neuronal K<sub>ATP</sub> channels was cell-autonomous and directly affected dentate granule neuron (DGN) excitability. To investigate the role of neuronal K<sub>ATP</sub> channels in the anticonvulsant effects of BAD, we imaged calcium during picrotoxin-induced epileptiform activity in entorhinal-hippocampal slices. BAD knockout reduced epileptiform activity, and this effect was lost upon knockout or pharmacological inhibition of K<sub>ATP</sub> channels. Targeted BAD knockout in DGNs alone was sufficient for the antiseizure effect in slices, consistent with a 'dentate gate' function that is reinforced by increased K<sub>ATP</sub> channel activity.
Medical subject headings
- Entorhinal Cortex
- KATP Channels
- Neurons
- Seizures
- bcl-Associated Death Protein