Title:Double-edged Role of KNa Channels in Brain Tuning: Identifying Epileptogenic
Network Micro-Macro Disconnection
Volume: 20
Issue: 5
Author(s): Ru Liu, Lei Sun, Yunfu Wang, Meng Jia, Qun Wang, Xiang Cai*Jianping Wu*
Affiliation:
- Advanced Innovation Center for Human Brain
Protection, Capital Medical University, Beijing, China
- Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain
Protection, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological
Diseases, Beijing, China
- School of Chemistry, Chemical
Engineering and Life Sciences, Wuhan University of Technology, Wuhan, China
Keywords:
Epilepsy, KNa channels, microcircuit, rhythm, micro-macro disconnection, quinidine.
Abstract: Epilepsy is commonly recognized as a disease driven by generalized hyperexcited and
hypersynchronous neural activity. Sodium-activated potassium channels (KNa channels), which are
encoded by the Slo 2.2 and Slo 2.1 genes, are widely expressed in the central nervous system and
considered as “brakes” to adjust neuronal adaptation through regulating action potential threshold or
after-hyperpolarization under physiological condition. However, the variants in KNa channels, especially
gain-of-function variants, have been found in several childhood epileptic conditions. Most
previous studies focused on mapping the epileptic network on the macroscopic scale while ignoring
the value of microscopic changes. Notably, paradoxical role of KNa channels working on individual
neuron/microcircuit and the macroscopic epileptic expression highlights the importance of understanding
epileptogenic network through combining microscopic and macroscopic methods. Here,
we first illustrated the molecular and physiological function of KNa channels on preclinical seizure
models and patients with epilepsy. Next, we summarized current hypothesis on the potential role of
KNa channels during seizures to provide essential insight into what emerged as a micro-macro disconnection
at different levels. Additionally, we highlighted the potential utility of KNa channels as
therapeutic targets for developing innovative anti-seizure medications.