astrocyte inositol triphosphate receptor type 2 and cytosolic phospholipase a2 alpha regulate arteriole responses in mouse neocortical brain slices2型星形胶质细胞三磷酸肌醇受体和胞质磷脂酶a2α调节小动脉反应在小鼠皮层脑片.pdfVIP

Astrocyte Inositol Triphosphate Receptor Type 2 and Cytosolic Phospholipase A2 Alpha Regulate Arteriole Responses in Mouse Neocortical Brain Slices 1 2 1 Lihua He , David J. Linden , Adam Sapirstein * 1 Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 2 Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America Abstract Functional hyperemia of the cerebral vascular system matches regional blood flow to the metabolic demands of the brain. One current model of neurovascular control holds that glutamate released by neurons activates group I metabotropic glutamate receptors (mGluRs) on astrocytes, resulting in the production of diffusible messengers that act to regulate smooth muscle cells surrounding cerebral arterioles. The acute mouse brain slice is an experimental system in which changes in arteriole diameter can precisely measured with light microscopy. Stimulation of the brain slice triggers specific cellular responses that can be correlated to changes in arteriole diameter. Here we used inositol trisphosphate receptor type 2 (IP R2) and cytosolic phospholipase A alpha (cPLA a) deficient mice to determine if astrocyte mGluR activation coupled 3 2 2 to IP R2-mediated Ca2+ release and subsequent cPLA a activation is required for arteriole regulation. We measured changes 3 2 in astrocyte cytosolic free Ca2+ and arteriole diameters in response to mGluR agonist or electrical field stimulation in acute neocortical mouse brain slices maintained in 95% or 20% O