6533b81ffe1ef96bd12771ab
RESEARCH PRODUCT
TRESK channel contributes to depolarization-induced shunting inhibition and modulates epileptic seizures.
Yue KeKewan WangJin CongJianping ZhuWerner KilbZhenhai ZhangWeiyuan HuangTian-ming GaoWenxiang MengHailin YeHeiko J. LuhmannRongqing ChenYanwu GuoShuai Liusubject
Potassium ChannelsAction PotentialsNeurotransmissionLigandsGeneral Biochemistry Genetics and Molecular BiologyIon ChannelsEpilepsyGlutamatergicPostsynaptic potentialSeizuresmedicinePotassium Channel BlockersAnimalsHumansRNA MessengerIon channelgamma-Aminobutyric AcidMice KnockoutNeuronsChemistryDepolarizationmedicine.diseaseMice Inbred C57BLHEK293 CellsGene Expression RegulationSynapsesCalciumNeuroscienceShunting inhibitionIonotropic effectdescription
Glutamatergic and GABAergic synaptic transmission controls excitation and inhibition of postsynaptic neurons, whereas activity of ion channels modulates neuronal intrinsic excitability. However, it is unclear how excessive neuronal excitation affects intrinsic inhibition to regain homeostatic stability under physiological or pathophysiological conditions. Here, we report that a seizure-like sustained depolarization can induce short-term inhibition of hippocampal CA3 neurons via a mechanism of membrane shunting. This depolarization-induced shunting inhibition (DShI) mediates a non-synaptic, but neuronal intrinsic, short-term plasticity that is able to suppress action potential generation and postsynaptic responses by activated ionotropic receptors. We demonstrate that the TRESK channel significantly contributes to DShI. Disruption of DShI by genetic knockout of TRESK exacerbates the sensitivity and severity of epileptic seizures of mice, whereas overexpression of TRESK attenuates seizures. In summary, these results uncover a type of homeostatic intrinsic plasticity and its underlying mechanism. TRESK might represent a therapeutic target for antiepileptic drugs.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-03-03 | Cell reports |