In the brain, increased neuronal activity evokes an increase in local cerebral blood flow. This neurovascular coupling is critical to the maintenance of cerebral homeostasis; however, the mechanism by which neuronal activity is communicated to the cerebral microcirculation is unclear. This proposal will investigate the requirement for astrocytic and smooth muscle large conductance calcium-activated potassium (BK) channels in mediating neuronal activity induced vasodilation and regulating vascular tone, respectively. Cortical brain slices will be used to study signaling between neurons, astrocytes and cerebral arterioles in a native cellular context. The mechanisms underlying cytosolic calcium ([Ca2+]c) signal generation in astrocytes will be investigated using confocal imaging. The ability of neurons to signal to arterioles in the absence of BK channel expression will be determined, as measured by vascular diameter and smooth muscle [Ca2+]c changes. Since abnormalities in the cerebral microcirculation have been associated with pathological conditions including stroke and migraine, elucidation of the signaling pathways which dynamically regulate arteriole diameter may aid in the development of novel clinical treatments for such disorders. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL083768-01
Application #
7058180
Study Section
Special Emphasis Panel (ZRG1-F03B (20))
Program Officer
Meadows, Tawanna
Project Start
2006-09-30
Project End
2008-09-29
Budget Start
2006-09-30
Budget End
2007-09-29
Support Year
1
Fiscal Year
2006
Total Cost
$48,796
Indirect Cost
Name
University of Vermont & St Agric College
Department
Pharmacology
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Straub, Stephen V; Girouard, Helene; Doetsch, Paul E et al. (2009) Regulation of intracerebral arteriolar tone by K(v) channels: effects of glucose and PKC. Am J Physiol Cell Physiol 297:C788-96
Straub, Stephen V; Nelson, Mark T (2007) Astrocytic calcium signaling: the information currency coupling neuronal activity to the cerebral microcirculation. Trends Cardiovasc Med 17:183-90
Straub, Stephen V; Bonev, Adrian D; Wilkerson, M Keith et al. (2006) Dynamic inositol trisphosphate-mediated calcium signals within astrocytic endfeet underlie vasodilation of cerebral arterioles. J Gen Physiol 128:659-69
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