Channelpedia

PubMed 25966943


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ2 , Kv7.2



Title: Protective role of Kv7 channels in oxygen and glucose deprivation-induced damage in rat caudate brain slices.

Authors: Vincenzo Barrese, Maurizio Taglialatela, Iain A Greenwood, Colin Davidson

Journal, date & volume: J. Cereb. Blood Flow Metab., 2015 Oct , 35, 1593-600

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25966943


Abstract
Ischemic stroke can cause striatal dopamine efflux that contributes to cell death. Since Kv7 potassium channels regulate dopamine release, we investigated the effects of their pharmacological modulation on dopamine efflux, measured by fast cyclic voltammetry (FCV), and neurotoxicity, in Wistar rat caudate brain slices undergoing oxygen and glucose deprivation (OGD). The Kv7 activators retigabine and ICA27243 delayed the onset, and decreased the peak level of dopamine efflux induced by OGD; and also decreased OGD-induced damage measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Retigabine also reduced OGD-induced necrotic cell death evaluated by lactate dehydrogenase activity assay. The Kv7 blocker linopirdine increased OGD-evoked dopamine efflux and OGD-induced damage, and attenuated the effects of retigabine. Quantitative-PCR experiments showed that OGD caused an ~6-fold decrease in Kv7.2 transcript, while levels of mRNAs encoding for other Kv7 subunits were unaffected; western blot experiments showed a parallel reduction in Kv7.2 protein levels. Retigabine also decreased the peak level of dopamine efflux induced by L-glutamate, and attenuated the loss of TTC staining induced by the excitotoxin. These results suggest a role for Kv7.2 in modulating ischemia-evoked caudate damage.