Tags

Type your tag names separated by a space and hit enter

Lamotrigine inhibits postsynaptic AMPA receptor and glutamate release in the dentate gyrus.
Epilepsia 2008; 49(5):888-97E

Abstract

PURPOSE

The dentate gyrus (DG) is a gateway that regulates seizure activity in the hippocampus. We investigated the site of action of lamotrigine (LTG), an effective anticonvulsant, in the regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptor-mediated excitatory synaptic transmission on DG.

METHODS

Evoked AMPA and NMDA receptor-mediated excitatory postsynaptic currents (eEPSCampa and eEPSCnmda) were recorded by whole-cell patch-clamp recording from the granule cells of DG in brain slice preparation of young Wistar rats (60-120 g). Exogenously applied AMPA and NMDA-induced currents and AMPA receptor-mediated miniature EPSC (mEPSCampa) were recorded in the presence of specific antagonists.

RESULTS

LTG inhibited both eEPSCampa and eEPSCnmda, and had no effect on exogenously applied NMDA-induced current indicating LTG inhibited glutamate release. Previous studies demonstrated that alteration in glutamate concentration in synaptic cleft causes parallel changes of eEPSCampa and eEPSCnmda. Our results showed that LTG inhibited eEPSCampa significantly more than eEPSCnmda (p < 0.05), suggesting that LTG may also have blocked the postsynaptic AMPA receptor. The hypothesis is further supported by the facts that; (1) LTG (30-100 microM) inhibited direct exogenously applied AMPA-induced currents (to 90%), (2) LTG significantly reduced the amplitude, but not the frequency of mEPSCampa and asynchronous (EPSC), and (3) LTG-induced reduction of eEPSCampa was not associated with a modification of the paired-pulse ratio. To sum up, LTG exerts a postsynaptic inhibitory mechanism on the AMPA receptor.

CONCLUSIONS

Our results demonstrate that LTG suppresses postsynaptic AMPA receptors and reduces glutamate release in granule cells of DG. The postsynaptic effect can be one of the underlying mechanisms of LTG's anticonvulsant action.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18248444

Citation

Lee, Chun-Yao, et al. "Lamotrigine Inhibits Postsynaptic AMPA Receptor and Glutamate Release in the Dentate Gyrus." Epilepsia, vol. 49, no. 5, 2008, pp. 888-97.
Lee CY, Fu WM, Chen CC, et al. Lamotrigine inhibits postsynaptic AMPA receptor and glutamate release in the dentate gyrus. Epilepsia. 2008;49(5):888-97.
Lee, C. Y., Fu, W. M., Chen, C. C., Su, M. J., & Liou, H. H. (2008). Lamotrigine inhibits postsynaptic AMPA receptor and glutamate release in the dentate gyrus. Epilepsia, 49(5), pp. 888-97. doi:10.1111/j.1528-1167.2007.01526.x.
Lee CY, et al. Lamotrigine Inhibits Postsynaptic AMPA Receptor and Glutamate Release in the Dentate Gyrus. Epilepsia. 2008;49(5):888-97. PubMed PMID: 18248444.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lamotrigine inhibits postsynaptic AMPA receptor and glutamate release in the dentate gyrus. AU - Lee,Chun-Yao, AU - Fu,Wen-Mei, AU - Chen,Chih-Chuan, AU - Su,Ming-Jai, AU - Liou,Horng-Huei, Y1 - 2008/01/29/ PY - 2008/2/6/pubmed PY - 2008/6/18/medline PY - 2008/2/6/entrez SP - 888 EP - 97 JF - Epilepsia JO - Epilepsia VL - 49 IS - 5 N2 - PURPOSE: The dentate gyrus (DG) is a gateway that regulates seizure activity in the hippocampus. We investigated the site of action of lamotrigine (LTG), an effective anticonvulsant, in the regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptor-mediated excitatory synaptic transmission on DG. METHODS: Evoked AMPA and NMDA receptor-mediated excitatory postsynaptic currents (eEPSCampa and eEPSCnmda) were recorded by whole-cell patch-clamp recording from the granule cells of DG in brain slice preparation of young Wistar rats (60-120 g). Exogenously applied AMPA and NMDA-induced currents and AMPA receptor-mediated miniature EPSC (mEPSCampa) were recorded in the presence of specific antagonists. RESULTS: LTG inhibited both eEPSCampa and eEPSCnmda, and had no effect on exogenously applied NMDA-induced current indicating LTG inhibited glutamate release. Previous studies demonstrated that alteration in glutamate concentration in synaptic cleft causes parallel changes of eEPSCampa and eEPSCnmda. Our results showed that LTG inhibited eEPSCampa significantly more than eEPSCnmda (p < 0.05), suggesting that LTG may also have blocked the postsynaptic AMPA receptor. The hypothesis is further supported by the facts that; (1) LTG (30-100 microM) inhibited direct exogenously applied AMPA-induced currents (to 90%), (2) LTG significantly reduced the amplitude, but not the frequency of mEPSCampa and asynchronous (EPSC), and (3) LTG-induced reduction of eEPSCampa was not associated with a modification of the paired-pulse ratio. To sum up, LTG exerts a postsynaptic inhibitory mechanism on the AMPA receptor. CONCLUSIONS: Our results demonstrate that LTG suppresses postsynaptic AMPA receptors and reduces glutamate release in granule cells of DG. The postsynaptic effect can be one of the underlying mechanisms of LTG's anticonvulsant action. SN - 0013-9580 UR - https://www.unboundmedicine.com/medline/citation/18248444/Lamotrigine_inhibits_postsynaptic_AMPA_receptor_and_glutamate_release_in_the_dentate_gyrus_ L2 - https://doi.org/10.1111/j.1528-1167.2007.01526.x DB - PRIME DP - Unbound Medicine ER -