Potassium buffering in the neurovascular unit

Models and sensitivity analysis

Alexandra Witthoft, Jessica Andrea Filosa, George Em Karniadakis

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Astrocytes are critical regulators of neural and neurovascular network communication. Potassium transport is a central mechanism behind their many functions. Astrocytes encircle synapses with their distal processes, which express two potassium pumps (Na-K and NKCC) and an inward rectifying potassium channel (Kir), whereas the vessel-adjacent endfeet express Kir and BK potassium channels. We provide a detailed model of potassium flow throughout the neurovascular unit (synaptic region, astrocytes, and arteriole) for the cortex of the young brain. Our model reproduces several phenomena observed experimentally: functional hyperemia, in which neural activity triggers astrocytic potassium release at the perivascular endfoot, inducing arteriole dilation; K+ undershoot in the synaptic space after periods of neural activity; neurally induced astrocyte hyperpolarization during Kir blockade. Our results suggest that the dynamics of the vascular response during functional hyperemia are governed by astrocytic Kir for the fast onset and astrocytic BK for maintaining dilation. The model supports the hypothesis that K+ undershoot is caused by excessive astrocytic uptake through Na-K and NKCC pumps, whereas the effect is balanced by Kir. We address parametric uncertainty using high-dimensional stochastic sensitivity analysis and identify possible model limitations.

Original languageEnglish (US)
Pages (from-to)2046-2054
Number of pages9
JournalBiophysical Journal
Volume105
Issue number9
DOIs
StatePublished - Nov 5 2013

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Astrocytes
Potassium
Potassium Channels
Hyperemia
Arterioles
Dilatation
Large-Conductance Calcium-Activated Potassium Channels
Sodium-Potassium-Exchanging ATPase
Synapses
Uncertainty
Blood Vessels
Brain

ASJC Scopus subject areas

  • Biophysics

Cite this

Potassium buffering in the neurovascular unit : Models and sensitivity analysis. / Witthoft, Alexandra; Filosa, Jessica Andrea; Karniadakis, George Em.

In: Biophysical Journal, Vol. 105, No. 9, 05.11.2013, p. 2046-2054.

Research output: Contribution to journalArticle

Witthoft, Alexandra ; Filosa, Jessica Andrea ; Karniadakis, George Em. / Potassium buffering in the neurovascular unit : Models and sensitivity analysis. In: Biophysical Journal. 2013 ; Vol. 105, No. 9. pp. 2046-2054.
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