Endothelial SKCa and IKCa Channels Regulate Brain Parenchymal Arteriolar Diameter and Cortical Cerebral Blood Flow

Calcium-sensitive potassium (K Ca ) channels have been shown to modulate the diameter of cerebral pial arteries; however, little is known regarding their roles in controlling cerebral parenchymal arterioles (PAs). We explored the function and cellular distribution of small-conductance (SK Ca ) and intermediate-conductance (IK Ca ) K Ca channels and large-conductance K Ca (BK Ca ) channels in endothelial cells (ECs) and smooth muscle cells (SMCs) of PAs. Both SK Ca and IK Ca channels conducted the outward current in isolated PA ECs (current densities, ~20 pA/pF and ~28 pA/pF at + 40 mV, respectively), but these currents were not detected in PA SMCs. In contrast, BK Ca currents were prominent in PA SMCs (~ 154pA/pF), but were undetectable in PA ECs. Pressurized PAs constricted to inhibition of SK Ca (~ 16%) and IK Ca (~ 16%) channels, but were only modestly affected by inhibition of BK Ca channels (~ 5%). Blockade of SK Ca and IK Ca channels decreased resting cortical cerebral blood flow (CBF) by ~ 15%. NS309 (6,7-dichloro-1H-indole-2,3-dione3-oxime), a SK Ca /IK Ca channel opener, hyperpolarized PA SMCs by ~ 27 mV, maximally dilated pressurized PAs, and increased CBF by ~ 40%. In conclusion, these data show that SK Ca and IK Ca channels in ECs profoundly modulate PA tone and CBF, whereas BK Ca channels in SMCs only modestly influence PA diameter.