Figure 2.

The mechanisms by which neurons and astrocytes stimulate arteriole and capillary dilation in response to synaptic activity. Synaptic activity increases intracellular Ca²⁺ levels within the postsynaptic neuron by stimulating metabotropic G-protein-coupled receptors (GPCRs), ionotropic receptors (e.g., NMDARs) or L-type voltage-operated Ca²⁺ channels (VOCs). This increase in [Ca²⁺]_i leads to the synthesis of NO and PGE2, which may relax both smooth muscle cells (arterioles) and pericytes (capillaries). Synaptically-released neurotransmitters may also increase [Ca²⁺]_i in perisynaptic astrocytes, thereby triggering NO release and PGE2/EET production. AA, which may be synthesized by PLA2 in both neurons and astrocytes, may be converted in the vasoconstricting factor, 20-HETE, in perivascular cells. Abbreviations: 20-HETE: 20-hydroxyeicosatetraenoic acid; AA: arachidonic acid; COX1: cyclooxygenase 1; COX2: cyclooxygenase 2; EETs: epoxyeicosatrienoic acids; GPCRs; G-protein-coupled receptors; InsP₃: inositol-1,4,5-trisphosphate; K_Ca: Ca²⁺-activated intermediate and small conductance K⁺ channels; NO: nitric oxide; nNOS: neuronal NO synthase; P450: cytochrome P450; PGE2: prostaglandin E2; PLA2: phospholipase A2; PLD2: phospholipase D2; VOCs: L-type voltage-operated Ca²⁺ channels.