Ischemia, whether in abrupt or chronic form, limits ATP production and disrupts ATP-dependent homeostatic mechanisms, leading to alterations in both intracellular and extracellular ion concentrations. In particular, extracellular potassium will spread locally and create cellular depolarization and depolarization blockade, the phenomenon of spreading depression (SD). Excess extracellular K+ produces additional energy demand from the Na+-K+-pump, producing a pathological confluence of increased energy demand with reduced energy delivery. These changes will have profound effects at subcellular, cellular, and network scales of brain function. We focused on the different consequences of ischemic/SD homeostatic failure on disjunct dendritic regions of a hippocampal CA1 pyramidal neuron, utilizing a mechanistic simulation with a full neuronal morphology with pumps and exchangers as well as voltage- and \ca-sensitive ion channels. We found that calcium accumulation was greatest in the basilar dendrites relative to the rest of the cell, suggesting that these dendrites would show the greatest effects of excitotoxicity. By contrast, distal apical dendrites were exposed to greater chloride concentrations, which is likely to lead to dendritic beading.
Model Type: Extracellular; Neuron or other electrically excitable cell
Region(s) or Organism(s): Hippocampus
Cell Type(s): Hippocampus CA1 pyramidal GLU cell
Currents: Ca pump; I Cl, leak; I K,leak; I Na, leak; I_SERCA; KCC2; Kir; NKCC1; Na+-glutamate transporter; Na/Ca exchanger; Na/K pump
Receptors:
Genes:
Transmitters: Glutamate
Model Concept(s): Homeostasis; Reaction-diffusion; Spreading depression
Simulation Environment: NEURON
References: