Paradoxical hyperexcitability from NaV1.2 sodium channel loss in neocortical pyramidal cells
Perry W.E. Spratt, Ryan P.D. Alexander, Roy Ben‐Shalom, Atehsa Sahagun, Henry Kyoung, Caroline M. Keeshen, Stephan Sanders, Kevin J. Bender
Abstract
1.2 loss prevented potassium channels from properly repolarizing neurons between APs, increasing overall excitability by allowing neurons to reach threshold for subsequent APs more rapidly. This cell-intrinsic mechanism may, therefore, account for why SCN2A loss-of-function can paradoxically promote seizure.
Topics & Concepts
NAV1NeocortexSodium channelExcitatory postsynaptic potentialNeuroscienceLoss functionPyramidal cellPotassium channelPatch clampEpilepsyBiologyElectrophysiologyChemistryBiophysicsSodiumGeneInhibitory postsynaptic potentialPhenotypeGeneticsHippocampal formationOrganic chemistryIon channel regulation and functionNeuroscience and Neuropharmacology ResearchCardiac electrophysiology and arrhythmias