The extent of anoxic depolarization (AD), the initial electrophysiological event during ischemia, determines the degree of brain region-specific neuronal damage. Neurons in higher brain regions have stronger ADs and are more easily injured than neurons in lower brain region. The mechanism leading to such differences is not clear. We use a computational model based on a Hodgkin-Huxley framework which includes neural spiking dynamics, processes of ion accumulation, and homeostatic mechanisms like vascular coupling and Na/K-exchange pumps. We show that a large extracellular space (ECS) explains the recovery failure in high brain regions. A phase-space analysis shows that with a large ECS recovery from AD through potassium regulation is impossible. The code 'time_series.ode' can be used to simulate AD for a large and a small ECS and show the different behaviors. The code ‘continuations.ode’ can be used to show the fixed point structure. Depending on our choice of large or small ECS the fixed point curve implies the presence/absence of a recovery threshold that defines the potassium clearance demand.
Model Type: Neuron or other electrically excitable cell
Cell Type(s): Abstract single compartment conductance based cell
Currents: I Chloride; I Na,t; I K; I K,leak; I h; I Sodium; I Potassium; I_K,Na; Na/K pump; I Cl, leak; I Na, leak
Model Concept(s): Action Potentials; Pathophysiology; Sodium pump; Depolarization block; Homeostasis; Potassium buffering
Simulation Environment: XPPAUT
References:
Hübel N, Andrew RD, Ullah G. (2016). Large extracellular space leads to neuronal susceptibility to ischemic injury in a Na+/K+ pumps-dependent manner. Journal of computational neuroscience. 40 [PubMed]