Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jul;72(7):1500-1515.
doi: 10.1007/s12031-022-02041-7. Epub 2022 Jul 12.

Molecular Mechanisms of Epilepsy: The Role of the Chloride Transporter KCC2

Giorgio Belperio  1 , Claudia Corso  1 , Carlos B Duarte  2   3 , Miranda Mele  4   5
Affiliations
Review

Molecular Mechanisms of Epilepsy: The Role of the Chloride Transporter KCC2

Giorgio Belperio et al. J Mol Neurosci. 2022 Jul.

Abstract

Epilepsy is a neurological disease characterized by abnormal or synchronous brain activity causing seizures, which may produce convulsions, minor physical signs, or a combination of symptoms. These disorders affect approximately 65 million people worldwide, from all ages and genders. Seizures apart, epileptic patients present a high risk to develop neuropsychological comorbidities such as cognitive deficits, emotional disturbance, and psychiatric disorders, which severely impair quality of life. Currently, the treatment for epilepsy includes the administration of drugs or surgery, but about 30% of the patients treated with antiepileptic drugs develop time-dependent pharmacoresistence. Therefore, further investigation about epilepsy and its causes is needed to find new pharmacological targets and innovative therapeutic strategies. Pharmacoresistance is associated to changes in neuronal plasticity and alterations of GABAA receptor-mediated neurotransmission. The downregulation of GABA inhibitory activity may arise from a positive shift in GABAA receptor reversal potential, due to an alteration in chloride homeostasis. In this paper, we review the contribution of K+-Cl--cotransporter (KCC2) to the alterations in the Cl- gradient observed in epileptic condition, and how these alterations are coupled to the increase in the excitability.

Keywords: Chloride homeostasis; Epilepsy; K+–Cl− co-transporter 2 (KCC2); Neuronal excitability.

PubMed Disclaimer

References

    1. Aguado F, Carmona MA, Pozas E, Aguilo A, Martinez-Guijarro FJ, Alcantara S et al (2003) BDNF regulates spontaneous correlated activity at early developmental stages by increasing synaptogenesis and expression of the K+/Cl- co-transporter KCC2. Development 130(7):1267–1280. https://doi.org/10.1242/dev.00351 - DOI - PubMed
    1. Akerman CJ, Cline HT (2006) Depolarizing GABAergic conductances regulate the balance of excitation to inhibition in the developing retinotectal circuit in vivo. J Neurosci 26(19):5117–5130. https://doi.org/10.1523/JNEUROSCI.0319-06.2006 - DOI - PubMed - PMC
    1. Akyuz E, Polat AK, Eroglu E, Kullu I, Angelopoulou E, Paudel YN (2021) Revisiting the role of neurotransmitters in epilepsy: an updated review. Life Sci 265:118826. https://doi.org/10.1016/j.lfs.2020.118826 - DOI - PubMed
    1. Albertson AJ, Yang J, Hablitz JJ (2011) Decreased hyperpolarization-activated currents in layer 5 pyramidal neurons enhances excitability in focal cortical dysplasia. J Neurophysiol 106(5):2189–2200. https://doi.org/10.1152/jn.00164.2011 - DOI - PubMed - PMC
    1. Anstotz M, Fiske MP, Maccaferri G (2021) Impaired KCC2 Function Triggers interictal-like activity driven by parvalbumin-expressing interneurons in the isolated subiculum in vitro. Cereb Cortex 31(10):4681–4698. https://doi.org/10.1093/cercor/bhab115 - DOI - PubMed - PMC