EPILEPTIC HUMAN DENTATE GYRUS GRANULE CELLS EXPRESS HIGH LEVELS OF THE HYPERPOLARIZATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED CHANNEL MOLECULES (HCNS)
Abstract number :
3.038
Submission category :
Year :
2002
Submission ID :
3379
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Roland A. Bender, Gary W. Mathern, Tallie Z. Baram. Anatomy/Neurobiology and Pediatrics, University of California, Irvine, CA; Division of Neurosurgery, Brain Research Institute and Mental Retardation Research Center, University of California, Los Angeles
RATIONALE: In the normal hippocampus, channels activated when neurons are hyperpolarized (HCNs), contribute to maintenance of cellular resting membrane potential and to synchronized activation of neuronal ensembles. Recent studies have suggested that [italic]abnormal[/italic] expression of HCNs may occur in an animal model of prolonged febrile seizures, and contribute to hippocampal hyperexcitability. However, whether these channel molecules are expressed in human epileptic hippocampus, and whether their expression correlates with clinical characteristics is unknown.
METHODS: Surgically-resected hippocampi (n=12) from patients with temporal lobe epilepsy (TLE), with (n=9) or without HS (n=3), were compared with autopsy cases (n=8). HCN mRNA expression was determined by both semi-quantitative and non-radioactive [italic]in situ[/italic] hybridization.
RESULTS: HCN1 mRNA was highly expressed in dentate gyrus granule cells of hippocampi resected from patients with TLE, whereas autopsy cases had no or little HCN1 mRNA expression. Preliminary analyses suggest that HCN expression was particularly prominent when GC cell loss was severe, but did not correlate with duration of epilepsy.
CONCLUSIONS: The novel and marked upregulation of HCN expression in human granule cells of TLE patients might signify an involvement of these channels in the epileptogenic process. Mechanisms for HCN upregulation may include the recurrent seizures (Brewster et al., J Neurosci, 2002) or the increased activation of these channels by aberrant GABAergic innervation (sprouting), and might constitute a compensatory mechanism, in attempt to attenuate the impact of dendritic excitatory input on granule cell firing (Poolos & Johnston, 2001). The implications of these data for epileptogenesis are under investigation.
[Supported by: EFA (RAB), NS02808 and NS38992 (GWM), NS35439 and NS28912 (TZB)]