RGD Reference Report - Activation of BKca channels mediates hippocampal neuronal death after reoxygenation and reperfusion. - Rat Genome Database

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Activation of BKca channels mediates hippocampal neuronal death after reoxygenation and reperfusion.

Authors: Chen, M  Sun, HY  Hu, P  Wang, CF  Li, BX  Li, SJ  Li, JJ  Tan, HY  Gao, TM 
Citation: Chen M, etal., Mol Neurobiol. 2013 Dec;48(3):794-807. doi: 10.1007/s12035-013-8467-x. Epub 2013 May 8.
RGD ID: 10412031
Pubmed: PMID:23653329   (View Abstract at PubMed)
DOI: DOI:10.1007/s12035-013-8467-x   (Journal Full-text)

Excessive K(+) efflux promotes central neuronal apoptosis; however, the type of potassium channel that mediates K(+) efflux in response to different apoptosis-inducing stimuli is still unknown. It is hypothesized that the activation of large-conductance Ca(2+)-activated K(+) channels (BKCa) mediates hypoxia/reoxygenation (H/R)- and ischemia/reperfusion (I/R)-induced neuronal apoptosis. Rat hippocampal neuronal cultures underwent apoptosis after reoxygenation, as assessed by morphologic observation, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and caspase-3 activation. Single-channel recordings revealed upregulation of BKCa channel activity 6 h after reoxygenation, which might be caused by elevated cytosolic Ca(2+). The K(+) ionophore valinomycin and the BKCa channel opener NS1619 induced neuronal apoptosis. Transfection of the BKCa channel alpha subunit into Chinese hamster ovary (CHO-K1) cells, which do not express endogenous K(+) channels, or into neurons will induce cell apoptosis, indicating that the opening of the BKCa channel serves as a pivotal event in mediating cell apoptosis. The specific BKCa channel blockers charybdotoxin and iberiotoxin and the nonselective K(+) channel blocker tetraethylammonium at concentrations more specific to the BKCa channel were neuroprotective. The A-type potassium channel blocker 4-aminopyridine and apamin, a small-conductance Ca(2+)-activated K(+) channel blocker, were not protective. This result suggests the involvement of the BKCa channel in H/R-induced apoptosis. Similarly, specific BKCa channel blockers also showed neuroprotection in neurons subjected to oxygen-glucose deprivation/reoxygenation or animals subjected to forebrain ischemia-reperfusion. These results demonstrate that the over-activity of BKCa channels mediates hippocampal neuronal damage induced by H/R in vitro and I/R in vivo.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of neuron apoptotic process  IMP 10412031 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kcnma1  (potassium calcium-activated channel subfamily M alpha 1)


Additional Information