title: Local potassium signaling couples neuronal activity to vasodilation in the brain.
abstract: 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.
authors.affiliation: Department of Pharmacology, 89 Beaumont Avenue, College of Medicine, University of Vermont, Burlington, Vermont 05405, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Filosa
authors.forename: Adrian D
authors.initials: AD
authors.lastname: Bonev
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Straub
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Meredith
authors.forename: M Keith
authors.initials: MK
authors.lastname: Wilkerson
authors.forename: Richard W
authors.initials: RW
authors.lastname: Aldrich
authors.forename: Mark T
authors.initials: MT
authors.lastname: Nelson
mesh_terms: D000818:Animals; D001160:Arterioles / Q000294:innervation / Q000502:physiology; D001253:Astrocytes / Q000502:physiology; D001921:Brain / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000294:innervation / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D011188:Potassium; D002118:Calcium