Modulation of Synaptic Kv4.2 in Hippocampus during Status Epilepticus
Abstract number :
3.003
Submission category :
Translational Research-Basic Mechanisms
Year :
2006
Submission ID :
6689
Source :
www.aesnet.org
Presentation date :
12/1/2006 12:00:00 AM
Published date :
Nov 30, 2006, 06:00 AM
Authors :
1Lyndon F. Barnwell, 2Yajun Ren, 2Joaquin N. Lugo Jr., and 1,2,3Anne E. Anderson
Kv4.2 subunits are thought to compose hippocampal A-type K+ channels, which regulate dendritic excitability in hippocampus. ERK activation via PKA and PKC downregulates dendritic A-type K+ currents and is associated with an increase in post-synaptic excitability. Direct ERK phosphorylation of Kv4.2 channel proteins is a candidate mechanism for this effect. We previously demonstrated a dramatic increase in ERK activation and phosphorylation of Kv4.2 acutely following kainate seizures. In the studies presented here we characterize the cellular localization of ERK activation and Kv4.2 regulation in hippocampus during status epilepticus (SE)., Seizures were induced in adult rats by kainate (KA) (15 mg/kg IP). Seizure activity was monitored and scored based on the Racine Scale. After 1-hr of SE animals were sacrificed for biochemical and molecular studies using whole cell homogenates, cellular membranes and synaptosomal preparations., Studies using hippocampal membrane preparations showed an increase in ERK-phosphorylated Kv4.2 (p[lt]0.05) while total Kv4.2 remained unchanged acutely following kainate-induced SE. This increase in Kv4.2 phosphorylation with SE was accompanied by increased ERK activation (p[lt]0.05) without a change in total ERK in membrane preparations. In parallel, using hippocampal synaptosomal preparations, we found increased ERK-phosphorylated Kv4.2 (p[lt]0.05) and ERK activation (p[lt]0.05) following SE. Intriguingly, levels of total Kv4.2 were significantly decreased (p[lt]0.05) in the synaptosomal preparations following acute SE. During this same time period, total ERK remained unchanged in the synaptosomal preparations. Studies are underway to evaluate the time-course of these changes in total Kv4.2 regulation and ERK signaling following convulsant stimulation., Our results reveal an increase in ERK-phosphorylated Kv4.2 channels and a decrease in total Kv4.2 proteins in the synaptosomal cellular compartment. The net effect of these changes is predicted to lead to an overall increase in hippocampal excitability during status epilepticus., (Supported by: Funded by NINDS/NIH, Society for Neuroscience, Pediatric Partnership for Epilepsy Research.)
Translational Research