Receptors with low affinity for neurosteroids and GABA contribute to tonic inhibition of granule cells in epileptic animals

摘要: Abstract Neurosteroid sensitivity of GABAA receptor mediated inhibition the hippocampal dentate granule cells (DGCs) is reduced in animal models temporal lobe epilepsy. However, properties and subunit composition receptors mediating tonic DGCs epileptic animals have not been described. In animals, allopregnanolone L-655708 holding current was diminished δ retained endoplasmic reticulum its surface expression decreased hippocampus. Ro15-4513 lanthanum had distinct effects on recorded from control suggesting that pharmacological maintaining were similar to those containing α4βxγ2 subunits. Furthermore, α4 increased a larger fraction co-immunoprecipitated with theγ2 hippocampi animals. Together, these studies revealed functional α4βxδ α5βxγ2 novel α4bxγ2 contributed maintenance inhibition. The presence resulted low GABA affinity neurosteroid currents could potentially increase seizure vulnerability. These may represent therapeutic target for anticonvulsant drugs without sedative actions.