Revisiting the Lamotrigine-Mediated Effect on Hippocampal GABAergic Transmission

Autor: Mong Lien Wang, Kaung Yi Chang, Yu Chao Liu, Yen-Chu Lin, Yi Ping Yang, Shih Hwa Chiou, Yu Yin Huang, Cheng Ta Lee
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Patch-Clamp Techniques
Action Potentials
Pharmacology
Hippocampal formation
Hippocampus
Synaptic Transmission
lcsh:Chemistry
Rats
Sprague-Dawley
0302 clinical medicine
voltage-gated sodium channel
lcsh:QH301-705.5
Spectroscopy
gamma-Aminobutyric Acid
Chemistry
Triazines
General Medicine
Computer Science Applications
Electrophysiology
GABAergic interneuron
Anesthesia
GABAergic
Anticonvulsants
medicine.drug
inhibitory postsynaptic current
Neurotransmission
Inhibitory postsynaptic potential
Lamotrigine
Catalysis
gamma-Aminobutyric acid
Article
Inorganic Chemistry
03 medical and health sciences
medicine
Animals
Channel blocker
Physical and Theoretical Chemistry
Molecular Biology
CA1 Region
Hippocampal
Dentate gyrus
Organic Chemistry
hyperpolarization-activated current
Rats
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Inhibitory Postsynaptic Potentials
030217 neurology & neurosurgery
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 17, Iss 7, p 1191 (2016)
International Journal of Molecular Sciences; Volume 17; Issue 7; Pages: 1191
ISSN: 1422-0067
Popis: Lamotrigine (LTG) is generally considered as a voltage-gated sodium (Nav) channel blocker. However, recent studies suggest that LTG can also serve as a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel enhancer and can increase the excitability of GABAergic interneurons (INs). Perisomatic inhibitory INs, predominantly fast-spiking basket cells (BCs), powerfully inhibit granule cells (GCs) in the hippocampal dentate gyrus. Notably, BCs express abundant Nav channels and HCN channels, both of which are able to support sustained action potential generation. Using whole-cell recording in rat hippocampal slices, we investigated the net LTG effect on BC output. We showed that bath application of LTG significantly decreased the amplitude of evoked compound inhibitory postsynaptic currents (IPSCs) in GCs. In contrast, simultaneous paired recordings from BCs to GCs showed that LTG had no effect on both the amplitude and the paired-pulse ratio of the unitary IPSCs, suggesting that LTG did not affect GABA release, though it suppressed cell excitability. In line with this, LTG decreased spontaneous IPSC (sIPSC) frequency, but not miniature IPSC frequency. When re-examining the LTG effect on GABAergic transmission in the cornus ammonis region 1 (CA1) area, we found that LTG markedly inhibits both the excitability of dendrite-targeting INs in the stratum oriens and the concurrent sIPSCs recorded on their targeting pyramidal cells (PCs) without significant hyperpolarization-activated current (Ih) enhancement. In summary, LTG has no effect on augmenting Ih in GABAergic INs and does not promote GABAergic inhibitory output. The antiepileptic effect of LTG is likely through Nav channel inhibition and the suppression of global neuronal network activity.
Databáze: OpenAIRE
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