Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow

Longden et al . demonstrate that brain capillaries function as a vast sensory web, monitoring neuronal activity by sensing K + and translating this into a K IR -channel-mediated regenerative retrograde hyperpolarizing signal that propagates to upstream arterioles to drive vasodilation and an increas...

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Vydáno v:	Nature neuroscience Ročník 20; číslo 5; s. 717 - 726
Hlavní autoři:	Longden, Thomas A, Dabertrand, Fabrice, Koide, Masayo, Gonzales, Albert L, Tykocki, Nathan R, Brayden, Joseph E, Hill-Eubanks, David, Nelson, Mark T
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.05.2017 Nature Publishing Group
Témata:	14/34 38/77 631/378/2607 631/443/592 64/60 9/30 9/74 Animal Genetics and Genomics Animals Behavioral Sciences Biological Techniques Biomedicine Blood vessels Brain Brain - blood supply Capillaries - physiology Endothelial Cells - physiology Male Membrane Potentials - physiology Mice Mice, Knockout Mice, Transgenic Neurobiology Neurons Neurosciences Potassium - physiology Potassium Channels, Inwardly Rectifying - genetics Potassium Channels, Inwardly Rectifying - physiology Sensors Vasodilation - physiology Veins & arteries
ISSN:	1097-6256, 1546-1726, 1546-1726
On-line přístup:	Získat plný text
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Abstract	Longden et al . demonstrate that brain capillaries function as a vast sensory web, monitoring neuronal activity by sensing K + and translating this into a K IR -channel-mediated regenerative retrograde hyperpolarizing signal that propagates to upstream arterioles to drive vasodilation and an increase in blood flow into the capillary bed. Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained unclear. Here we demonstrate a central role for capillary endothelial cells in sensing neural activity and communicating it to upstream arterioles in the form of an electrical vasodilatory signal. We further demonstrate that this signal is initiated by extracellular K + —a byproduct of neural activity—which activates capillary endothelial cell inward-rectifier K + (K IR 2.1) channels to produce a rapidly propagating retrograde hyperpolarization that causes upstream arteriolar dilation, increasing blood flow into the capillary bed. Our results establish brain capillaries as an active sensory web that converts changes in external K + into rapid, 'inside-out' electrical signaling to direct blood flow to active brain regions.
AbstractList	Longden et al . demonstrate that brain capillaries function as a vast sensory web, monitoring neuronal activity by sensing K + and translating this into a K IR -channel-mediated regenerative retrograde hyperpolarizing signal that propagates to upstream arterioles to drive vasodilation and an increase in blood flow into the capillary bed. Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained unclear. Here we demonstrate a central role for capillary endothelial cells in sensing neural activity and communicating it to upstream arterioles in the form of an electrical vasodilatory signal. We further demonstrate that this signal is initiated by extracellular K + —a byproduct of neural activity—which activates capillary endothelial cell inward-rectifier K + (K IR 2.1) channels to produce a rapidly propagating retrograde hyperpolarization that causes upstream arteriolar dilation, increasing blood flow into the capillary bed. Our results establish brain capillaries as an active sensory web that converts changes in external K + into rapid, 'inside-out' electrical signaling to direct blood flow to active brain regions. Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained unclear. Here we demonstrate a central role for capillary endothelial cells in sensing neural activity and communicating it to upstream arterioles in the form of an electrical vasodilatory signal. We further demonstrate that this signal is initiated by extracellular K -a byproduct of neural activity-which activates capillary endothelial cell inward-rectifier K (K 2.1) channels to produce a rapidly propagating retrograde hyperpolarization that causes upstream arteriolar dilation, increasing blood flow into the capillary bed. Our results establish brain capillaries as an active sensory web that converts changes in external K into rapid, 'inside-out' electrical signaling to direct blood flow to active brain regions. Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained unclear. Here we demonstrate a central role for capillary endothelial cells in sensing neural activity and communicating it to upstream arterioles in the form of an electrical vasodilatory signal. We further demonstrate that this signal is initiated by extracellular K+ -a byproduct of neural activity-which activates capillary endothelial cell inward-rectifier K+ (KIR2.1) channels to produce a rapidly propagating retrograde hyperpolarization that causes upstream arteriolar dilation, increasing blood flow into the capillary bed. Our results establish brain capillaries as an active sensory web that converts changes in external K+ into rapid, 'inside-out' electrical signaling to direct blood flow to active brain regions.Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained unclear. Here we demonstrate a central role for capillary endothelial cells in sensing neural activity and communicating it to upstream arterioles in the form of an electrical vasodilatory signal. We further demonstrate that this signal is initiated by extracellular K+ -a byproduct of neural activity-which activates capillary endothelial cell inward-rectifier K+ (KIR2.1) channels to produce a rapidly propagating retrograde hyperpolarization that causes upstream arteriolar dilation, increasing blood flow into the capillary bed. Our results establish brain capillaries as an active sensory web that converts changes in external K+ into rapid, 'inside-out' electrical signaling to direct blood flow to active brain regions. Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained unclear. Here we demonstrate a central role for capillary endothelial cells in sensing neural activity and communicating it to upstream arterioles in the form of an electrical vasodilatory signal. We further demonstrate that this signal is initiated by extracellular K+ --a byproduct of neural activity--which activates capillary endothelial cell inward-rectifier K+ (KIR 2.1) channels to produce a rapidly propagating retrograde hyperpolarization that causes upstream arteriolar dilation, increasing blood flow into the capillary bed. Our results establish brain capillaries as an active sensory web that converts changes in external K+ into rapid, 'inside-out' electrical signaling to direct blood flow to active brain regions.
Author	Longden, Thomas A Koide, Masayo Tykocki, Nathan R Gonzales, Albert L Brayden, Joseph E Hill-Eubanks, David Nelson, Mark T Dabertrand, Fabrice
Author_xml	– sequence: 1 givenname: Thomas A surname: Longden fullname: Longden, Thomas A organization: Department of Pharmacology, University of Vermont – sequence: 2 givenname: Fabrice surname: Dabertrand fullname: Dabertrand, Fabrice organization: Department of Pharmacology, University of Vermont – sequence: 3 givenname: Masayo surname: Koide fullname: Koide, Masayo organization: Department of Pharmacology, University of Vermont – sequence: 4 givenname: Albert L surname: Gonzales fullname: Gonzales, Albert L organization: Department of Pharmacology, University of Vermont – sequence: 5 givenname: Nathan R surname: Tykocki fullname: Tykocki, Nathan R organization: Department of Pharmacology, University of Vermont – sequence: 6 givenname: Joseph E surname: Brayden fullname: Brayden, Joseph E organization: Department of Pharmacology, University of Vermont – sequence: 7 givenname: David surname: Hill-Eubanks fullname: Hill-Eubanks, David organization: Department of Pharmacology, University of Vermont – sequence: 8 givenname: Mark T surname: Nelson fullname: Nelson, Mark T email: mark.nelson@uvm.edu organization: Department of Pharmacology, University of Vermont, Institute of Cardiovascular Sciences, University of Manchester
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/28319610$$D View this record in MEDLINE/PubMed
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Snippet	Longden et al . demonstrate that brain capillaries function as a vast sensory web, monitoring neuronal activity by sensing K + and translating this into a K IR... Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained...
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SubjectTerms	14/34 38/77 631/378/2607 631/443/592 64/60 9/30 9/74 Animal Genetics and Genomics Animals Behavioral Sciences Biological Techniques Biomedicine Blood vessels Brain Brain - blood supply Capillaries - physiology Endothelial Cells - physiology Male Membrane Potentials - physiology Mice Mice, Knockout Mice, Transgenic Neurobiology Neurons Neurosciences Potassium - physiology Potassium Channels, Inwardly Rectifying - genetics Potassium Channels, Inwardly Rectifying - physiology Sensors Vasodilation - physiology Veins & arteries
Title	Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow
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