AI Article Synopsis
- Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults, and understanding the role of voltage-gated chloride channels (ClC) in its development is crucial.
- Research showed that ClC-mediated currents were elevated in the hippocampal neurons of mice with chronic TLE, and blocking these channels with specific drugs reduced seizure frequency and enhanced inhibitory signaling.
- Increased expression of ClC-3 was observed in both TLE mice and patients, indicating its potential involvement in the mechanisms of epilepsy and suggesting that inhibiting ClC could be a promising treatment strategy.
Article 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).
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365373 | PMC |
| http://dx.doi.org/10.1016/j.ebiom.2021.103537 | DOI Listing |
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