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The Journal of neuroscience : the official journal of the Society for Neuroscience

Epilepsy-Associated KCNQ2 Channels Regulate Multiple Intrinsic Properties of Layer 2/3 Pyramidal Neurons.


PMID 28100740

Abstract

KCNQ2 potassium channels are critical for normal brain function, as both loss-of-function and gain-of-function KCNQ2 variants can lead to various forms of neonatal epilepsy. Despite recent progress, the full spectrum of consequences as a result of KCNQ2 dysfunction in neocortical pyramidal neurons is still unknown. Here, we report that conditional ablation of Kcnq2 from mouse neocortex leads to hyperexcitability of layer 2/3 (L2/3) pyramidal neurons, exhibiting an increased input resistance and action potential frequency, as well as a reduced medium afterhyperpolarization (mAHP), a conductance partly mediated by KCNQ2 channels. Importantly, we show that introducing the KCNQ2 loss-of-function variant KCNQ2 KCNQ2 channels are critical for the development of normal brain function, as KCNQ2 variants could lead to epileptic encephalopathy. However, the role of KCNQ2 channels in regulating the properties of neocortical neurons is largely unexplored. Here, we find that Kcnq2 ablation or loss-of-function at subthreshold membrane potentials leads to increased neuronal excitability of neocortical layer 2/3 (L2/3) pyramidal neurons. We also demonstrate that Kcnq2 ablation unexpectedly leads to a larger action potential amplitude. Importantly, we propose the Na

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