Astrocytic Kir4.1 channel and O 2 account for the transition dynamics between seizure-like discharges and spreading...

Both experiments and clinical studies have emphasized the complex interplay between astrocytic Kir4.1 channel and oxygen in regulating seizure-like discharges and spreading depression exhibited by neuron, particularly focusing on their transitional behaviors. However, how astrocytic Kir4.1 conductance and oxygen collaborate to regulate these transitional behaviors remains unclear. Here we proposed a three-compartment model that includes a neuron, an astrocyte, and their extracellular coupling space. This model was designed to explore the effects of astrocytic Kir4.1 conductance and oxygen concentration on the development of seizure-like discharges and spreading depression, as well as the intricate mechanisms underlying dynamical transitions. The simulation results demonstrated that Kir4.1 channel conductance and oxygen levels regulate various neuronal transition phenomena, including special seizures (SZ), tonic-seizures (TS), spreading depression, steady state (SS), tonic firing (TF) and mixed states (MS) involving seizure-like discharges and spreading depression, as defined in this study. And bifurcation analysis of a simplified model is employed to elucidate these internal transition mechanisms. The insights garnered from the proposed model can offer valuable perspectives into the functional intricacies of the brain and its pathological mechanisms.