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Cited by 522Barrier Structure and Function StudiesIon channel regulation and functionTraumatic Brain Injury and Neurovascular Disturbances

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

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Longden, Thomas A, Dabertrand, Fabrice, Koide, Masayo, Gonzales, Albert L, Tykocki, Nathan R, Brayden, Joseph E, Hill-Eubanks, David, Nelson, Mark T·2017·Nature Neuroscience
DOI 10.1038/nn.4533PMC PMC5404963
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Abstract

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.

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  • Capillary endothelial cells express voltage-gated K+ channel KV1 and the inward rectifier K+ channel KIR2.

    “Capillary endothelial cells express voltage-gated K + channel KV1 and the inward rectifier K + channel KIR2 (318, 374, 408, 666).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [374]

    The Results section, “Brain cECs express KIR2 channels,” reports KIR2-characteristic currents in mouse brain capillary endothelial cells, and the Discussion says these cells possess functional KIR2 channels. The passages do not establish expression of voltage-gated KV1 channels in those cells; searches for “Kv1” and “voltage-gated potassium channels capillary endothelial cells” found no supporting passage. Page numbers were not available in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • During physiological conditions, capillary endothelial K+ channels mediate outward K+ currents causing endothelial cell hyperpolarization that propagates vasodilatory signals upstream to arterioles, contributing to blood flow regulation.

    “During physiological conditions, capillary endothelial K + channels mediate outward K + currents causing endothelial cell hyperpolarization that propagates vasodilatory signals upstream to arterioles contributing to blood flow regulation (374, 375).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [374]

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Research works printed but not linked: 47

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Cited by

Sorted by citations

Authors
Longden, T. A., Dabertrand, F., Koide, M., Gonzales, A. L., Tykocki, N. R., Brayden, J. E., Hill-Eubanks, D., & Nelson, M. T.
Affiliations
University of Vermont (US)
Corresponding author
Nelson, Mark T
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2017-03-20
Volume
20
Issue
5
Pages
717-726
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/nn.4533
PMC
PMC5404963
OpenAlex
W2602561729
Cited by
522
References
3
Citations by year
2026: 46 · 2025: 65 · 2024: 62 · 2023: 60 · 2022: 55 · 2021: 70 · 2020: 67 · 2019: 38 · 2018: 45 · 2017: 13 · 2015: 1
FWCI
22.20
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion)
Funders
  • American Heart Association (14POST20480144)
  • National Institutes of Health (1s10od010583-01, 5p30gm103498-05)
  • National Heart, Lung, and Blood Institute (P01HL095488, R01HL121706, R01HL131181, T32HL007594, UM1HL120877, R01HL136636)
  • National Institute of General Medical Sciences (P30-GM103498)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R37DK053832, K01DK103840)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
regional cerebral blood flow, capillary endothelial cells, inwardly rectifying potassium channels, Kir2.1, electrical signaling, arteriolar vasodilation, cerebrovascular regulation
MeSH terms
Animals, Brain, Capillaries, Male, Membrane Potentials, Mice, Transgenic, Potassium, Vasodilation, Mice, Knockout, Potassium Channels, Inwardly Rectifying, Endothelial Cells, Mice

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