Ion channel networks in the control of cerebral blood flow
Open accessAbstract
One hundred and twenty five years ago, Roy and Sherrington made the seminal observation that neuronal stimulation evokes an increase in cerebral blood flow.(1) Since this discovery, researchers have attempted to uncover how the cells of the neurovascular unit-neurons, astrocytes, vascular smooth muscle cells, vascular endothelial cells and pericytes-coordinate their activity to control this phenomenon. Recent work has revealed that ionic fluxes through a diverse array of ion channel species allow the cells of the neurovascular unit to engage in multicellular signaling processes that dictate local hemodynamics.In this review we center our discussion on two major themes: (1) the roles of ion channels in the dynamic modulation of parenchymal arteriole smooth muscle membrane potential, which is central to the control of arteriolar diameter and therefore must be harnessed to permit changes in downstream cerebral blood flow, and (2) the striking similarities in the ion channel complements employed in astrocytic endfeet and endothelial cells, enabling dual control of smooth muscle from either side of the blood-brain barrier. We conclude with a discussion of the emerging roles of pericyte and capillary endothelial cell ion channels in neurovascular coupling, which will provide fertile ground for future breakthroughs in the field.
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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 [375]
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The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease
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Blood-Brain Barrier: From Physiology to Disease and Back
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Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain
Howard, P. G., Zou, P., Zhang, Y., Huang, F., Tesic, V., Wu, C. Y.-C., & Lee, R. H.-C. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114973 · Cited by 13 · see citing works
- Authors
- Longden, T. A., Hill-Eubanks, D. C., & Nelson, M. T.
- Affiliations
- University of Vermont (US)
- Department of Pharmacology, University of Vermont, Burlington, VT, USA
- Corresponding author
- Nelson, Mark T
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2015-11-09
- Volume
- 36
- Issue
- 3
- Pages
- 492-512
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC4794103
- OpenAlex
- W2288834750
- Cited by
- 137
- References
- 7
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 10 · 2023: 13 · 2022: 16 · 2021: 17 · 2020: 12 · 2019: 14 · 2018: 18 · 2017: 16 · 2016: 7
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL095488, R01HL121706)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK053832)
- National Center for Research Resources (P20-RR16435, P20RR016435)
- 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
- ion channels, cerebral blood flow, neurovascular unit, neurovascular coupling, arteriolar smooth muscle, astrocytes, astrocytic endfeet, endothelial cells, pericytes, capillary endothelial cells, blood-brain barrier, local hemodynamics
- MeSH terms
- Animals, Arterioles, Astrocytes, Blood-Brain Barrier, Brain, Cerebrovascular Circulation, Humans, Ion Channels, Membrane Potentials, Muscle, Smooth, Vascular, Calcium Signaling
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