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Ca 2+ ‐permeable AMPA receptors associated with epileptogenesis of hypothalamic hamartoma
Author(s) -
Kitaura Hiroki,
Sonoda Masaki,
Teramoto Sayaka,
Shirozu Hiroshi,
Shimizu Hiroshi,
Kimura Tadashi,
Masuda Hiroshi,
Ito Yosuke,
Takahashi Hitoshi,
Kwak Shin,
Kameyama Shigeki,
Kakita Akiyoshi
Publication year - 2017
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13700
Subject(s) - ampa receptor , epileptogenesis , gelastic seizure , glutamate receptor , receptor , nmda receptor , neuroscience , chemistry , biology , medicine , epilepsy , endocrinology , hypothalamic hamartoma , biochemistry , precocious puberty , hormone
Summary Hypothalamic hamartoma (HH), composed of neurons and glia without apparent cytologic abnormalities, is a rare developmental malformation in humans. Patients with HH often have characteristic medically refractory gelastic seizures, and intrinsic epileptogenesis within the lesions has been speculated. Herein we provide evidence to suggest that in HH neurons, Ca 2+ permeability through α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors is aberrantly elevated. In needle biopsy specimens of HH tissue, field potential recordings demonstrated spontaneous epileptiform activities similar to those observed in other etiologically distinct epileptogenic tissues. In HH, however, these activities were clearly abolished by application of Joro Spider Toxin (JSTX), a specific inhibitor of the Ca 2+ ‐permeable AMPA receptor. Consistent with these physiologic findings, the neuronal nuclei showed disappearance of adenosine deaminase acting on RNA 2 (ADAR2) immunoreactivity. Furthermore, examination of glutamate receptor 2 (GluA2) messenger RNA (mRNA) revealed that editing efficiency at the glutamine/arginine site was significantly low. These results suggest that neurons in HH may bear Ca 2+ ‐permeable AMPA receptors due to dislocation of ADAR2.