Module 7: Figure astrocyte endfoot signalling

Astrocyte regulation of cerebral blood flow.

When the intracellular Ca2+ wave spreads down into the astrocyte endfoot, it activates a number of signalling mechanisms that can alter smooth muscle cell (SMC) tone and hence the flow of blood through the arterioles. The nature of these signalling pathways are still being worked out, and the different astrocytes may use different mechanisms. One mechanism seems to depend on the activation of the large-conductance (BK) Ca2+-dependent channels, which release K+ that depolarizes the SMC to inhibit the Ca2+ oscillator, resulting in vessel dilation. Another mechanism is for Ca2+ to activate phospholipase A2 (PLA2) that hydrolyses phospholipids (PLs) to produce arachidonic acid (AA), which can have two actions. It can diffuse across to the SMC to be converted into the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE), or it can be converted by cyclooxygenase into PGE2, which then acts on PGE2 receptors (EP receptors) to inhibit muscle tone.