RRC ID 6633
Author Ohno Y, Sofue N, Ishihara S, Mashimo T, Sasa M, Serikawa T.
Title Scn1a missense mutation impairs GABAA receptor-mediated synaptic transmission in the rat hippocampus.
Journal Biochem. Biophys. Res. Commun.
Abstract Mutations of the Na(v)1.1 channel subunit SCN1A have been implicated in the pathogenesis of human febrile seizures (FS). We have recently developed hyperthermia-induced seizure-susceptible (Hiss) rat, a novel rat model of FS, which carries a missense mutation (N1417H) in Scn1a[1]. Here, we conducted electrophysiological studies to clarify the influences of the Scn1a mutation on the hippocampal synaptic transmission, specifically focusing on the GABAergic system. Hippocampal slices were prepared from Hiss or F344 (control) rats and maintained in artificial cerebrospinal fluid saturated with 95% O(2) and 5% CO(2)in vitro. Single neuron activity was recorded from CA1 pyramidal neurons and their responses to the test (unconditioned) or paired pulse (PP) stimulation of the Schaffer collateral/commissural fibers were evaluated. Hiss rats were first tested for pentylenetetrazole-induced seizures and confirmed to show high seizure susceptibility to the blockade of GAGA(A) receptors. The Scn1a mutation in Hiss rats did not directly affect spike generation (i.e., number of evoked spikes and firing threshold) of the CA1 pyramidal neurons elicited by the Schaffer collateral/commissural stimulation. However, GABA(A) receptor-mediated inhibition of pyramidal neurons by the PP stimulation was significantly disrupted in Hiss rats, yielding a significant increase in the number of PP-induced firings at PP intervals of 32-256ms. The present study shows that the Scn1a missense mutation preferentially impairs GABA(A) receptor-mediated synaptic transmission without directly altering the excitability of the pyramidal neurons in the hippocampus, which may be linked to the pathogenesis of FS.
Volume 400(1)
Pages 117-22
Published 2010-9-10
DOI 10.1016/j.bbrc.2010.08.021
PII S0006-291X(10)01507-X
PMID 20707984
MeSH Animals Convulsants / pharmacology Glutamate Decarboxylase / metabolism Hippocampus / drug effects Hippocampus / physiology* Mutation, Missense NAV1.1 Voltage-Gated Sodium Channel Nerve Tissue Proteins / genetics Nerve Tissue Proteins / physiology* Pentylenetetrazole / pharmacology Rats Rats, Inbred F344 Rats, Mutant Strains Receptors, GABA-A / physiology* Seizures, Febrile / chemically induced Seizures, Febrile / genetics* Seizures, Febrile / physiopathology Sodium Channels / genetics Sodium Channels / physiology* Synaptic Transmission / genetics*
IF 2.559
Times Cited 5
Rats F344-Scn1am1Kyo(strainID=716)