Reference - Detail
| RRC ID | 76 |
|---|---|
| Author | Yan HD, Ishihara K, Serikawa T, Sasa M. |
| Title | Activation by N-acetyl-L-aspartate of acutely dissociated hippocampal neurons in rats via metabotropic glutamate receptors. |
| Journal | Epilepsia |
| Abstract |
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 nM to 1 mM 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 approximately 0 mV. The NAA-induced current was inhibited by bath application of the metabotropic glutamate receptor (mGluR) antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG) and by intracellular application of guanosine 5'-O-(2-thiodiphosphate) (GDP-betaS), 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, CdCl2, 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. |
| Volume | 44(9) |
| Pages | 1153-9 |
| Published | 2003-9-1 |
| DOI | 10.1046/j.1528-1157.2003.49402.x |
| PII | 49402 |
| PMID | 12919386 |
| MeSH | Action Potentials / drug effects* Action Potentials / physiology Animals Aspartic Acid / analogs & derivatives* Aspartic Acid / pharmacology* Aspartic Acid / toxicity Dose-Response Relationship, Drug Epilepsy / chemically induced Epilepsy / physiopathology Hippocampus / cytology Hippocampus / drug effects* Hippocampus / physiology In Vitro Techniques Neurons / cytology Neurons / drug effects* Neurons / physiology Rats Rats, Wistar Receptors, Metabotropic Glutamate / physiology* |
| IF | 6.04 |
| Times Cited | 40 |
| WOS Category | CLINICAL NEUROLOGY |
| Resource | |
| Rats | |