Astrocytic endfoot Ca2+ and BK channels determine both arteriolar dilation and constriction.
Neuronal activity is thought to communicate to arterioles in the brain through astrocytic calcium (Ca(2+)) signaling to cause local vasodilation. Paradoxically, this communication may cause vasoconstriction in some cases. Here, we show that, regardless of the mechanism by which astrocytic endfoot Ca(2+) was elevated, modest increases in Ca(2+) induced dilation, whereas larger increases switched dilation to constriction. Large-conductance, Ca(2+)-sensitive potassium channels in astrocytic endfeet mediated a majority of the dilation and the entire vasoconstriction, implicating local extracellular K(+) as a vasoactive signal for both dilation and constriction. These results provide evidence for a unifying mechanism that explains the nature and apparent duality of the vascular response, showing that the degree and polarity of neurovascular coupling depends on astrocytic endfoot Ca(2+) and perivascular K(+).
Department of Pharmacology, University of Vermont, Burlington, VT 05405, USA.
Hélène
H
Girouard
Adrian D
AD
Bonev
Rachael M
RM
Hannah
Andrea
A
Meredith
Richard W
RW
Aldrich
Mark T
MT
Nelson
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000098:blood supply; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D020013:Calcium Signaling; D002560:Cerebrovascular Circulation; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D014661:Vasoconstriction; D014664:Vasodilation
D051036:Large-Conductance Calcium-Activated Potassium Channels; D011188:Potassium; D002118:Calcium