Sci. STKE, 14 September 2004
BRAIN Astrocytes Regulate Cerebral Blood Flow
Mulligan and MacVicar used two-photon laser scanning microscopy to selectively increase intracellular calcium concentration ([Ca2+]i) in astrocytes surrounding the arterioles in brain slices. Localized flash photolysis of caged calcium was used to increase [Ca2+]i in astrocytes identified by expression of green fluorescent protein (GFP) from an astrocyte-specific promoter. When a large amplitude increase in [Ca2+]i occurred in the astrocyte endfeet (the part that surrounds the blood vessel), arteriole constriction was observed. The extent of arteriole constriction correlated with the number of endfeet of the astrocyte into which the increase in [Ca2+]i propagated and vasoconstriction occurred after the increase in astrocyte [Ca2+]i. Noradrenergic neurons form synapses on the astrocyte endfeet, and norepinephrine (NE) causes vasoconstriction and reduced cerebral blood flow. Bath application or local application of NE produced large increases in [Ca2+]i within astrocyte endfeet and caused vasoconstriction. Vasoconstriction stimulated by astrocytic calcium photolysis was blocked by pharmacologic inhibition of astrocytic phospholipase A2 (PLA2) or pharmacologic inhibition of smooth muscle production of the eicosanoid 20-hydroxy eicosatetraenoic acid (20-HETE). 20-HETE blocks calcium-activated K+ channels and leads to membrane depolarization and smooth muscle calcium influx and contraction. The authors propose that increased astrocytic [Ca2+]i activates PLA2 and produces arachidonic acid, which diffuses into the vasculature smooth muscle and is converted into the vasoconstrictive 20-HETE. Peppiatt and Attwell discuss this new model in the context of previously proposed mechanisms for regulation of cerebral blood flow.
S. J. Mulligan, B. A. MacVicar, Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature 431, 95-99 (2004). [Online Journal]
C. Peppiatt, D. Attwell, Feeding the brain. Nature 431, 137-138 (2004). [Online Journal]
Citation: Astrocytes Regulate Cerebral Blood Flow. Sci. STKE 2004, tw324 (2004).
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