Potassium Channelopathies of Epilepsy

Channelopathies are inherited genetic changes in ion channel genes that generate a disease. Given the pivotal role of voltage-dependent potassium channels in moderating neuronal excitability, it is not surprising that these channels are well represented among the channelopathies contributing to epilepsy. Voltage-dependent potassium channels are regarded as the “initial responders” that shape and moderate depolarization of excitability cells. However, this oversimpli! cation belies a heterogeneous mix of diverse voltage-dependent potassium channels in the nervous system that are specialized for function in different subcellular compartments, in different neuronal types, and, indeed, even at different voltages. Consistent with this, the uncovering INTRODUCTION WHAT ARE POTASSIUM CHANNELS? KCNA1 Effect of KCNA1 Epilepsy Mutations on Potassium Currents KCNA1 and Sudden Unexplained Death in Epilepsy KCNA1 Channelopathy as a Consequence of LGI1 Mutations KCND2 KCND2 Channelopathy Mutation Acquired Changes in KCND2 and Seizures KCNMA1 KCNMA1 Gating Properties BK Channel Function in Neurons BK Channels and Acquired Epilepsy Human BK Channel Epilepsy Channelopathy KCNQ Channelopathy Mutations KCNQ Mutations and Animal Models KCNQ1 KCNJ10 KCNJ11 CONCLUSIONS