Extracellular Potassium and Focal Seizures—Insight from In Silico Study

Suffczyński, Piotr; Gentiletti, Damiano; Gnatkovsky, Vadym; Curtis, Marco de

doi:10.1007/978-3-319-49959-8_3

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“…The observation that the development of seizures may be related to an increase in [K + ] o beyond the physiological values suggests that the modulation of [K + ] o by the use of K + chelators is a potential strategy for the control of seizures. Moreover, in our previous work, we demonstrated that an artificial potassium buffer, which mimicked the function of astrocytes by balancing neuronal K + release, could reduce neuronal excitability and prevent an SLE (Suffczynski et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Focal seizures are organized by feedback between neural activity and ion concentration changes

Gentiletti

Gnatkovsky

et al. 2021

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Human and animal EEG data demonstrate that focal seizures start with low-voltage fast activity, evolve into rhythmic burst discharges and are followed by a period of suppressed background activity. This suggests that processes with dynamics in the range of tens of seconds govern focal seizure evolution. We investigate the processes associated with seizure dynamics by complementing the Hodgkin-Huxley mathematical model with the physical laws that dictate ion movement and maintain ionic gradients. We show that the disturbance of K+ and Cl− homeostasis by the fast discharge of inhibitory interneurons is sufficient to initiate seizures, which are maintained by positive feedback between ion concentration changes and neuronal activity. Gradual Na+ accumulation increases the rate of the Na+/K+-pump, creating negative feedback which slows down and terminates ictal discharges and contributes to the postictal state. Our results emphasize ionic dynamics as elementary processes behind seizure generation and indicate targets for new therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%