TY - JOUR
T1 - Potassium buffering in the neurovascular unit
T2 - Models and sensitivity analysis
AU - Witthoft, Alexandra
AU - Filosa, Jessica A.
AU - Karniadakis, George Em
N1 - Funding Information:
This work was supported by the National Science Foundation Office of Cyber Infrastructure (0904288) and National Institutes of Health National Heart, Lung and Blood Institute (R01 HL089067-02).
PY - 2013/11/5
Y1 - 2013/11/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bpj.2013.09.012
DO - 10.1016/j.bpj.2013.09.012
M3 - Article
C2 - 24209849
AN - SCOPUS:84887398435
SN - 0006-3495
VL - 105
SP - 2046
EP - 2054
JO - Biophysical Journal
JF - Biophysical Journal
IS - 9
ER -