Local potassium signaling couples neuronal activity to vasodilation in the brain.
The mechanisms by which active neurons, via astrocytes, rapidly signal intracerebral arterioles to dilate remain obscure. Here we show that modest elevation of extracellular potassium (K+) activated inward rectifier K+ (Kir) channels and caused membrane potential hyperpolarization in smooth muscle cells (SMCs) of intracerebral arterioles and, in cortical brain slices, induced Kir-dependent vasodilation and suppression of SMC intracellular calcium (Ca2+) oscillations. Neuronal activation induced a rapid (<2 s latency) vasodilation that was greatly reduced by Kir channel blockade and completely abrogated by concurrent cyclooxygenase inhibition. Astrocytic endfeet exhibited large-conductance, Ca2+-sensitive K+ (BK) channel currents that could be activated by neuronal stimulation. Blocking BK channels or ablating the gene encoding these channels prevented neuronally induced vasodilation and suppression of arteriolar SMC Ca2+, without affecting the astrocytic Ca2+ elevation. These results support the concept of intercellular K+ channel-to-K+ channel signaling, through which neuronal activity in the form of an astrocytic Ca2+ signal is decoded by astrocytic BK channels, which locally release K+ into the perivascular space to activate SMC Kir channels and cause vasodilation.
Filosa
Jessica A
JA
Department of Pharmacology, 89 Beaumont Avenue, College of Medicine, University of Vermont, Burlington, Vermont 05405, USA.
Bonev
Adrian D
AD
Straub
Stephen V
SV
Meredith
Andrea L
AL
Wilkerson
M Keith
MK
Aldrich
Richard W
RW
Nelson
Mark T
MT
D000818:Animals; D001160:Arterioles / Q000294:innervation / Q000502:physiology; D001253:Astrocytes / Q000502:physiology; D001921:Brain / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000294:innervation / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D024661:Potassium Channels, Inwardly Rectifying; D011188:Potassium; D002118:Calcium