Next Article in Journal
Nutritional Strategies for the Individualized Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) Based on the Nutrient-Induced Insulin Output Ratio (NIOR)
Previous Article in Journal
Orofacial Manifestations and Temporomandibular Disorders of Systemic Scleroderma: An Observational Study
Open AccessArticle

Revisiting the Lamotrigine-Mediated Effect on Hippocampal GABAergic Transmission

1
Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan
2
Department of Anesthesiology, Cheng Hsin General Hospital, Taipei 112, Taiwan
3
Institute of Neuroscience and Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan
4
Institute of Pharmacology, National Yang-Ming University, Taipei 112, Taiwan
5
Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan
6
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 112, Taiwan
7
Department of Anesthesiology, Taipei Veterans General Hospital, Taipei 112, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Masatoshi Maki
Int. J. Mol. Sci. 2016, 17(7), 1191; https://doi.org/10.3390/ijms17071191
Received: 14 June 2016 / Accepted: 19 July 2016 / Published: 22 July 2016
(This article belongs to the Section Biochemistry)
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. View Full-Text
Keywords: Lamotrigine; GABAergic interneuron; inhibitory postsynaptic current; voltage-gated sodium channel; hyperpolarization-activated current Lamotrigine; GABAergic interneuron; inhibitory postsynaptic current; voltage-gated sodium channel; hyperpolarization-activated current
Show Figures

Figure 1

MDPI and ACS Style

Huang, Y.-Y.; Liu, Y.-C.; Lee, C.-T.; Lin, Y.-C.; Wang, M.-L.; Yang, Y.-P.; Chang, K.-Y.; Chiou, S.-H. Revisiting the Lamotrigine-Mediated Effect on Hippocampal GABAergic Transmission. Int. J. Mol. Sci. 2016, 17, 1191.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map

1
Back to TopTop