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Activation by N ‐Acetyl‐ l ‐Aspartate of Acutely Dissociated Hippocampal Neurons in Rats via Metabotropic Glutamate Receptors
Author(s) -
Yan HaiDun,
Ishihara Kumatoshi,
Serikawa Tadao,
Sasa Masashi
Publication year - 2003
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.2003.49402.x
Subject(s) - metabotropic glutamate receptor , glutamate receptor , neuroscience , metabotropic glutamate receptor 5 , hippocampal formation , metabotropic receptor , metabotropic glutamate receptor 2 , chemistry , metabotropic glutamate receptor 7 , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 6 , metabotropic glutamate receptor 4 , metabotropic glutamate receptor 3 , receptor , psychology , biochemistry
Summary: Purpose: We previously reported that an increase in the N ‐acetyl‐ l ‐aspartate (NAA) level due to the lack of aspartoacylase gene was found in the brain of the tremor rat ( tm/tm ), which is a mutant with a causative gene named tm that shows epileptic seizures. Therefore, NAA is suggested to be one of the factors involved in the induction of epileptic seizures. Patch‐clamp studies were performed to determine whether NAA produces an excitatory effect on acutely dissociated rat hippocampal neurons. Methods: Acutely dissociated hippocampal neurons were prepared from normal Wistar rats aged 3–4 weeks. NAA‐induced currents were investigated by using the whole‐cell voltage‐clamp recording technique. Results : Application of NAA at concentrations of 100 n M to 1 m M through a U‐tube for 2 s produced an inward current in a concentration‐dependent manner at a holding potential of –60 mV. When the current–voltage relation was examined, the reversal potential of the NAA‐induced current was found to be ∼0 mV. The NAA‐induced current was inhibited by bath application of the metabotropic glutamate receptor (mGluR) antagonist (±)‐α‐methyl‐4‐carboxyphenylglycine (MCPG) and by intracellular application of guanosine 5′‐ O ‐(2‐thiodiphosphate) (GDP‐βS), a nonhydrolyzable GDP analogue. However, the NAA‐induced current remained unaffected by glutamic acid diethyl ester, a non– N ‐methyl‐ d ‐aspartate (NMDA)‐subtype ionotropic glutamate receptor antagonist, or the voltage‐dependent ion channel blockers tetrodotoxin, CdCl 2 , and tetraethylammonium‐chloride. Conversely, the mGluR agonist, trans ‐(1S,3R)‐1‐amino‐1,3‐cyclopentanedicarboxylic acid (ACPD) also induced an inward current, with a reversal potential of 0 mV. The ACPD‐induced current also was inhibited by MCPG. Conclusions: These results suggest that NAA acts on the G protein‐coupled mGluRs to induce an inward current that results in excitation of the neurons, thereby contributing to the occurrence of epileptic seizures.