Necrotic insults such as @entity410 are excitotoxic. Logically, membrane hyperpolarization by increasing outwardly conducting @entity972 channel currents should attenuate hyperexcitation and enhance neuron survival. Therefore, we overexpressed a small-conductance @entity460 -activated ( @entity31858 ) or voltage-gated ( @entity9400 ) channel via viral vectors in cultured hippocampal neurons. We found that @entity31858 or @entity9400 protected not only against @entity4176 or @entity2227 excitotoxicity but also increased survival after @entity17376 or @entity866 . In vivo overexpression of either channel in dentate gyrus reduced @entity4176 -induced @entity1400 lesions. In hippocampal slices, the @entity4176 -induced increase in granule cell excitability was reduced by overexpression of either channel, suggesting that these channels exert their protective effects during hyperexcitation. It is also important to understand any functional disturbances created by transgene overexpression alone. In the absence of insult, overexpression of @entity9400 , but not @entity31858 , reduced baseline excitability in dentate gyrus granule cells. Furthermore, while no behavioral disturbances during spatial acquisition in the Morris water maze were observed with overexpression of either channel, animals overexpressing @entity31858 , but not @entity9400 , exhibited a memory deficit post-training. This difference raises the possibility that the means by which these channel subtypes protect may differ. With further development, @entity972 channel vectors may be an effective pre-emptive strategy against @entity39 .

XXXX channel gene therapy can prevent neuron death resulting from necrotic and apoptotic insults.

@entity1400 :: ('761', 'Gene') :: ['CA3'] @entity410 :: ('MESH:D012640', 'Disease') :: ['seizure'] @entity2227 :: ('CHEBI:29987', 'Chemical') :: ['glutamate'] @entity39 :: ('MESH:D009336', 'Disease') :: ['necrotic insults'] @entity31858 :: ('3781', 'Gene') :: ['SK2'] @entity9400 :: ('3736', 'Gene') :: ['Kv1.1'] @entity4176 :: ('MESH:D007608', 'Chemical') :: ['kainate'] @entity866 :: ('MESH:D019311', 'Chemical') :: ['staurosporine'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity972 :: ('MESH:D011188', 'Chemical') :: ['potassium'] @entity17376 :: ('MESH:D012966', 'Chemical') :: ['sodium cyanide']
@entity972 :: (MESH:D011188,Chemical) :: ['Potassium']
