Figure 3: Schematic model liking SAH to inversion of neurovascular coupling. In control animals, EFS causes elevated cytoplasmic Ca2+ in astrocytes leading to increased BK channel activity and modest (<20 mM) increases in perivascular K+, promoting vasodilation. SAH increases the magnitude of spontaneous astrocytic Ca2+ oscillations and basal activity of BK channels, elevating K+ in restricted perivascular space. The summation of increased basal perivascular K+ and “normal” nerve-evoked astrocyte BK channel activity results in extracellular K+ concentrations that exceed the dilation-constriction threshold (~20 mM), inducing vasoconstriction. BK: large conductance Ca2+-activated K+ channel, CBF: cerebral blood flow, EFS: electrical field stimulation, Glu: glutamate, Kir: inward rectifier K+ channel, mGluR: metabotropic glutamate receptor, VDCC: voltage-dependent Ca2+ channel (modified from Koide et al. [21]).