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© Thomas Longden

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Capillary control of brain blood flow

Longden T, Dabertrand F, Koide M, Gonzales A, Tykocki N, Brayden J, Hill-Eubanks D, Nelson M (2017) “Capillary K+-sensing initiates retrograde hyperpolarization to locally increase cerebral blood flow” Nature Neuroscience20: 717-726.

This paper reveals a novel mechanism by which capillaries control brain blood flow. We show that capillaries sense potassium released during neuronal activity, and translate this into a Kir channel-mediated rapidly-propagating retrograde hyperpolarization. This 'inverted action potential' dilates upstream arterioles to increase blood flow to the underlying capillary bed.

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Harraz O, Longden T, Hill-Eubanks D, Nelson M (2018) "PIP2 depletion promotes TRPV4 channel activity in mouse brain capillary endothelial cellseLife. 7: e38689.

 

Harraz O, Longden T, Dabertrand F, Hill-Eubanks D, Nelson M (2018) "Endothelial GqPCR activity controls capillary electrical signaling and brain blood flow through PIP2 depletion"Proceedings of the National Academy of Sciences USA. 115: E3569-E3577.

Tykocki N, Bonev A, Longden T, Heppner T, Nelson M (2017) “Inhibition of vascular smooth muscle inward-rectifier K+ channels restores myogenic tone in mouse urinary bladder arterioles” American Journal of Physiology Renal Physiology, 312(5):F836-F847.

Longden T, Hill-Eubanks D, Nelson M (2016) “Ion Channel Networks in the Control of Cerebral Blood Flow” Journal of Cerebral Blood Flow & Metabolism, 36(3):492-512.

Klitgaard-Povlsen G, Longden T, Bonev A, Hill-Eubanks D, Nelson M (2016) “Uncoupling of Neurovascular Communication After Transient Global Cerebral Ischemia is Caused by Impaired Parenchymal Smooth Muscle KIRChannel Function” Journal of Cerebral Blood Flow & Metabolism, 36(7):1195-1201.

Longden T, Nelson M (2015) “Vascular Inward Rectifier K+ Channels as External K+ Sensors in the Control of Cerebral Blood Flow.” Microcirculation, 22(3): 183-196.

Balbi M, Ghosh M, Longden T, Vega M, Gesierich B, Hellal F, Lourbopoulos A, Nelson M, Plesnila N (2015) “Dysfunction of mouse cerebral arteries during early aging” Journal of Cerebral Blood Flow & Metabolism35(9): 1445-1453.

Villalba N, Sonkusare S, Longden T, Tran T, Sackheim A, Nelson M, Wellman G, Freeman K (2014) “Traumatic brain injury disrupts cerebrovascular tone through endothelial inducible nitric oxide synthase expression and nitric oxide gain of function.” Journal of the American Heart Association, 3(6): e001474.

Longden T, Dabertrand F, Hill-Eubanks D, Hammack S, Nelson M (2014) “Stress-Induced Glucocorticoid Signaling Remodels Neurovascular Coupling Through Impairment of Cerebrovascular Inwardly Rectifying K+Channel Function.” Proceedings of the National Academy of Sciences USA, 111(20): 7462-7.

Longden T, Dunn K, Draheim H, Nelson M, Weston A, Edwards G (2011) “Intermediate-Conductance Calcium-Activated Potassium Channels Participate in Neurovascular Coupling.” British Journal of Pharmacology, 164(3): 922-33.