Figure 1.

Multicompartment distribution of free Ca²⁺ hypothesized in the brain in vivo during the baseline conditions (A–C) and evoked neural activity conditions (D–F) based on in vitro literature on Ca²⁺ measurements from neurons, glia, and brain slices.^{2, 4, 5, 7, 8, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25} (D) During normal physiologic conditions, evoked brain activity can decrease extracellular and endoplasmic reticular Ca²⁺ ranges, and increase cytoplasmic and mitochondria Ca²⁺ ranges. (E) During mCU inhibition, evoked activity can lead to a relatively smaller decrease in extracellular and endoplasmic reticular (ER) Ca²⁺ ranges and smaller increase in cytoplasmic and mitochondrial Ca²⁺ ranges. Accumulating microdomain Ca²⁺ may inhibit plasma membrane glutamate receptors and mobilization from the ER stores resulting in reduced cytoplasmic Ca²⁺. This leads to the hypothesis that diminished mitochondrial Ca²⁺ influx capacity will reduce neocortical excitability, metabolism, and hemodynamic response. (F) During mCU enhancement, evoked activity can lead to relatively larger decreases in extracellular and ER Ca²⁺ ranges and relatively larger increases in cytoplasmic and mitochondrial Ca²⁺ ranges. Augmented clearance of Ca²⁺ in the microdomains by mitochondria may delay the Ca²⁺-mediated N-methyl-D-aspartate receptor desensitization resulting in larger cytoplasmic Ca²⁺ ranges. This leads to the hypothesis that enhanced mitochondrial Ca²⁺ influx capacity will increase neocortical excitability, metabolism, and hemodynamic response.