Bibliographic Details
| Title: |
Abnormal γ-aminobutyric acid neurotransmission in a Kcnq2 model of early onset epilepsy. |
| Authors: |
Uchida, Taku, Lossin, Christoph, Ihara, Yukiko, Deshimaru, Masanobu, Yanagawa, Yuchio, Koyama, Susumu, Hirose, Shinichi |
| Source: |
Epilepsia (Series 4); Aug2017, Vol. 58 Issue 8, p1430-1439, 10p |
| Subject Terms: |
GENETICS of epilepsy, AMINOBUTYRIC acid, NEURAL transmission, GENETIC mutation, NEONATAL diseases |
| Abstract: |
Objective Mutations of the KCNQ2 gene, which encodes the Kv7.2 subunit of voltage-gated M-type potassium channels, have been associated with epilepsy in the neonatal period. This developmental stage is unique in that the neurotransmitter gamma aminobutyric acid (GABA), which is inhibitory in adults, triggers excitatory action due to a reversed chloride gradient. Methods To examine whether KCNQ2-related neuronal hyperexcitability involves neonatally excitatory GABA, we examined 1-week-old knockin mice expressing the Kv7.2 variant p.Tyr284Cys (Y284C). Results Brain slice electrophysiology revealed elevated CA1 hippocampal GABAergic interneuron activity with respect to presynaptic firing and postsynaptic current frequency. Blockade with the GABAA receptor antagonist bicuculline decreased ictal-like bursting in brain slices with lowered divalent ion concentration, which is consistent with GABA mediating an excitatory function that contributes to the hyperexcitability observed in mutant animals. Significance We conclude that excitatory GABA contributes to the phenotype in these animals, which raises the question of whether this special type of neurotransmission has broader importance in neonatal epilepsy than is currently recognized. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
