KCNQ potassium channels as Key Players of Homeostatic Plasticity and Epilepsy.  Add To Calendar

Speaker: Hee Jung Chung, University of Illinois at Urbana-Champaign
Host: Richmond
  • Date(s): Thursday, 4/13 4:00 PM to Thursday, 4/13 5:00 PM
  • Campus Address: 4289 SEL, 840 West Taylor St



Epilepsy is a chronic brain disorder that strikes over 2% of the world population. It is caused by neuronal hyperexcitability clinically characterized as seizures. While 40% of epilepsy is associated with genetic mutations, the cause for the rest of epilepsy (acquired epilepsy) is unclear. To understand the pathogenesis of epilepsy, our lab focuses on investigating early-onset epilepsy mutations in Kv7/KCNQ potassium channels that potently inhibit repetitive and burst firing of action potentials. I will present our recent identification of epilepsy mutation hotspots in Kv7.2 and Kv7.3 subunits, one of which mediates calmodulin binding. Our lab has discovered that calmodulin binding is critical for the channels to enrich at the axonal plasma membrane whereas familial epilepsy mutations disrupt this regulation. Interestingly, de novo severe symptomatic epileptic encephalopathy mutations in this domain cause multiple dysfunctions of Kv7 channel expression, localization, and voltage-dependent activation, which led to neuronal hyperexcitability and death.  Our lab also investigates the hypothesis that acquired epilepsy is in part caused by abnormal regulation of homeostatic plasticity, a mechanism by which neurons adapt their electrical activity within a physiologic range based on their previous activity. For example, 2-day blockade of neuronal activity in the hippocampus leads to compensatory increase in synaptic transmission and intrinsic excitability, whereas activity blockade for 2-4 weeks leads to temporal lobe epilepsy in rodents.  In addition to identifying activity-regulated transcripts during homeostatic plasticity, we showed that homeostatic scaling in hippocampal excitability are associated with repression of multiple potassium channel genes and a decrease in total potassium current, including the currents through axonal Kv1 and Kv7 channels. Remarkably, this scaling involves upstream signaling pathways and transcription profiles that are distinct from homeostatic scaling of excitatory synaptic transmission. We have begun to address how such distinct regulation occurs, honing into excitatory synapses and the axonal initial segment, the site of action potential generation and regulation. Website