Back to Search
Start Over
The role of voltage-gated chloride channels in the epileptogenesis of temporal lobe epilepsy
- Source :
- EBioMedicine, Vol 70, Iss, Pp 103537-(2021), EBioMedicine
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Background Temporal lobe epilepsy (TLE) is the most common intractable epilepsy in adults, and elucidation of the underlying pathological mechanisms is needed. Voltage-gated chloride channels (ClC) play diverse physiological roles in neurons. However, less is known regarding their functions in the epilepogenesis of TLE. Methods ClC-mediated current and the spontaneous inhibitory synaptic currents (sIPSC) in hippocampal neurons of epileptic lesions were investigated by electrophysiological recording. The EEG data were analyzed by Z-scored wavelet and Fourier transformations. The expression of ClC-3, a member of ClC gene family, was detected by immunostaining and western blot. Findings ClC-mediated current was increased in the hippocampal neurons of chronic TLE mice. Application of chloride channel blockers, NPPB (5-Nitro-2- [3-phenylpropylamino] benzoic acid) and DIDS (4,4’-Diisothiocyanato-2,2’-stilbenedisulfonic acid disodium salt) reduced ClC-mediated current and increased inhibitory synaptic transmission in TLE mice. NPPB and DIDS reduced the seizure frequency and the average absolute power of ictal high-frequency oscillations (HFOs, 80-500 Hz) in TLE mice. In addition, both drugs induced outwardly rectified currents, which might be tonic inhibitory currents in the hippocampal neurons of TLE patients. Furthermore, the expression of ClC-3 was increased in the hippocampus of TLE mice and patients and positively correlated with both the absolute power and number of ictal HFOs per seizure in the sclerotic hippocampus. Interpretation These data suggest that ClC participate in the epilepogenetic process of TLE and the inhibition of ClC may have anti-epileptic effect. Funding This work was supported by National Natural Science Foundation of China (No. 81601143, No. 81771217).
- Subjects :
- Adult
Male
Medicine (General)
Research paper
Hippocampus
Chloride channel blockers
Hippocampal formation
Neurotransmission
Inhibitory postsynaptic potential
Epileptogenesis
General Biochemistry, Genetics and Molecular Biology
Mice
Epilepsy
R5-920
Chloride Channels
Voltage-gated chloride channels
medicine
Animals
Humans
Ictal
Temporal lobe epilepsy
High-frequency oscillations
urogenital system
Chemistry
General Medicine
medicine.disease
nervous system diseases
Mice, Inbred C57BL
Electrophysiology
Epilepsy, Temporal Lobe
Inhibitory Postsynaptic Potentials
nervous system
Medicine
Female
Neuroscience
Subjects
Details
- ISSN :
- 23523964
- Volume :
- 70
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....324496f876497fbe449bb88e8bab72a5