(The FASEB Journal. 2008;22:lb634)
© 2008 FASEB
Roles of BK and Kir channels in the coupling of neural activity to vasodilation in the somatosensory cortex in vivo
Helene Girouard1,
Andrea L. Meredith2,
Richard Aldrich3 and
Mark T. Nelson1
1 Pharmacology, University of Vermont, South Burlington, VT,
2 Physiology, University of Maryland, Baltimore, MD,
3 Neurobiology, University of Texas at Austin, Austin, TX
ABSTRACT
One mechanism to couple neuronal activity to vasodilation in the cortex is through the activation of large-conductance, calcium-sensitive potassium (BK) channels in astrocytic endfeet, which in turn through potassium release stimulates arteriolar smooth muscle (SM) inward rectifier potassium (Kir) channels (Nature Neuroscience, 2006). This mechanism has several in vivo implications for neurovascular coupling (NVC), measured as whisker stimulated increases in local cerebral blood flow (CBF) by laser-Doppler flowmetry in anesthetized mice. Inhibitors of BK (paxilline) and Kir (barium) channels attenuated CBF increases in response to whisker stimulation by 56% and 45%, respectively, in a non additive manner. Crippling BK channel function in the SM by targeted disruption of the gene for the auxiliary beta1 subunit attenuated the effect of paxilline by 25% without significantly affecting the response to barium. Ablation of the gene for pore-forming alpha subunit of the BK channel prevented the actions of paxilline and barium. These results support the concept that astrocytic BK and SM Kir channels act in series to translate neuronal activity into vasodilation and indicate a small participation of SM BK channels in NVC. We conclude that the astrocytic BK-SM Kir pathway plays a significant physiological role in NVC.
