| Popis: |
Neuroinflammation associated with CNS insults leads to neuronal hyperexcitability, which may culminate in epileptiform discharges.Application of the endotoxin lipopolysaccharide (LPS) to brain tissue initiates a neuroinflammatory cascade, providing an experimental model to study the mechanisms of neuroinflammatory neuronal hyperexcitability.Here we show that LPS application to hippocampal slices markedly enhances the excitability of CA1 pyramidal cells by inhibiting a specific potassium current, the M‐current, generated by KV7/M channels, which controls the excitability of almost every neuron in the CNS.The LPS‐induced M‐current inhibition is triggered by sequential activation of microglia, astrocytes and pyramidal cells, mediated by metabotropic purinergic and glutamatergic transmission, leading to blockade of KV7/M channels by calcium released from intracellular stores.The identification of the downstream molecular target of neuroinflammation, namely the KV7/M channel, potentially has far reaching implications for the understanding and treatment of many acute and chronic brain disorders. |
