Nature Neuroscience
- 9, 1397 - 1403 (2006)
Published online: 1 October 2006; | doi:10.1038/nn1779
Local potassium signaling couples neuronal activity to vasodilation in the brainJessica A Filosa1, 2, Adrian D Bonev1, Stephen V Straub1, Andrea L Meredith3, 4, M Keith Wilkerson1, Richard W Aldrich3, 4 & Mark T Nelson11
Department of Pharmacology, 89 Beaumont Avenue, College of Medicine, University of Vermont, Burlington, Vermont 05405, USA. 2
Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio 45237, USA. 3
Department of Molecular and Cellular Physiology and the Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA. 4
Present addresses: Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street (BRB5), Baltimore, Maryland 21201, USA (A.L.M.) and Section of Neurobiology, 1 University Station C7000, University of Texas at Austin, Austin, Texas 78712, USA (R.W.A.).
Correspondence should be addressed to Mark T Nelson Mark.Nelson@uvm.edu The mechanisms by which active neurons, via astrocytes, rapidly signal intracerebral arterioles to dilate remain obscure. Here we show that modest elevation of extracellular potassium (K+) activated inward rectifier K+ (Kir) channels and caused membrane potential hyperpolarization in smooth muscle cells (SMCs) of intracerebral arterioles and, in cortical brain slices, induced Kir-dependent vasodilation and suppression of SMC intracellular calcium (Ca2+) oscillations. Neuronal activation induced a rapid (<2 s latency) vasodilation that was greatly reduced by Kir channel blockade and completely abrogated by concurrent cyclooxygenase inhibition. Astrocytic endfeet exhibited large-conductance, Ca2+-sensitive K+ (BK) channel currents that could be activated by neuronal stimulation. Blocking BK channels or ablating the gene encoding these channels prevented neuronally induced vasodilation and suppression of arteriolar SMC Ca2+, without affecting the astrocytic Ca2+ elevation. These results support the concept of intercellular K+ channel–to–K+ channel signaling, through which neuronal activity in the form of an astrocytic Ca2+ signal is decoded by astrocytic BK channels, which locally release K+ into the perivascular space to activate SMC Kir channels and cause vasodilation.
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