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

Abstract
Calcium-sensitive potassium (KCa) 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 (SKCa) and intermediate-conductance (IKCa) KCa channels and large-conductance KCa (BKCa) channels in endothelial cells (ECs) and smooth muscle cells (SMCs) of PAs. Both SKCa and IKCa 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, BKCa currents were prominent in PA SMCs (~ 154pA/pF), but were undetectable in PA ECs. Pressurized PAs constricted to inhibition of SKCa (~ 16%) and IKCa (~ 16%) channels, but were only modestly affected by inhibition of BKCa channels (~ 5%). Blockade of SKCa and IKCa channels decreased resting cortical cerebral blood flow (CBF) by ~ 15%. NS309 (6,7-dichloro-1...