Neuroprotective Effect of KR-31378 via KATP Channel Opening against Ischemic Insult

The opening of the adenosine triphosphate (ATP)–sensitive potassium (KATP) channel has been proposed as a therapeutic approach for ischemia. Here we examined the opening effect of KR-31378 on the KATP channel using patch clamp recording in neuroblastoma 2a (N2a) cells and investigated the neuroprote...

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Bibliographic Details
Published in:Biological & Pharmaceutical Bulletin 2004, Vol.27(8), pp.1285-1288
Main Authors: Won, Ran, Lim, Jong-Yoon, Lee, Sang-Yeon, Park, Ji-Ho, Sohn, Nak-Won
Format: Article
Language:eng ; jpn
Subjects:
Animals
Brain Ischemia - prevention & control
Cell Line, Tumor
glibenclamide
Guanidines - pharmacology
KR-31378
Mice
Neuroprotective Agents - pharmacology
Organ Culture Techniques
organotypic slice culture
oxygen/glucose deprivation
patch-clamp
Patch-Clamp Techniques
Potassium Channels, Inwardly Rectifying - drug effects
Potassium Channels, Inwardly Rectifying - physiology
Pyrans - pharmacology
Rats
Rats, Sprague-Dawley
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Summary:The opening of the adenosine triphosphate (ATP)–sensitive potassium (KATP) channel has been proposed as a therapeutic approach for ischemia. Here we examined the opening effect of KR-31378 on the KATP channel using patch clamp recording in neuroblastoma 2a (N2a) cells and investigated the neuroprotective effect of KR-31378 in organotypic hippocampal slice cultures exposed to oxygen/glucose deprivation. The treatment with KR-31378 (10 μM) to N2a cells seemed to induce KATP channel opening in a dose dependent manner. The opening effect of KR-31378 was more significant than that of other known KATP channel openers. Pretreatment with KR-31378 (10 μM) showed a neuroprotective effect in both CA1 and CA3 regions and its effect was attenuated by glibenclamide in a dose dependent manner in both areas. This remarkable neuroprotective effect of KR-31378 seemed to be mediated by the opening of the KATP channel. These results suggest that KR-31378 could be a possible neuroprotective agent against cerebral ischemia.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.27.1285