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 (SKCa) and intermediate-conductance (IKCa) K-Ca channels and large-conductance K-Ca (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, similar to 20 pA/pF and similar to 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 (similar to 154 pA/pF), but were undetectable in PA ECs. Pressurized PAs constricted to inhibition of SKCa (similar to 16%) and IKCa (similar to 16%) channels, but were only modestly affected by inhibition of BKCa channels (similar to 5%). Blockade of SKCa and IKCa channels decreased resting cortical cerebral blood flow (CBF) by similar to 15%. NS309 (6,7-dichloro-1H-indole-2,3-dione3-oxime), a SKCa/IKCa channel opener, hyperpolarized PA SMCs by similar to 27mV, maximally dilated pressurized PAs, and increased CBF by similar to 40%. In conclusion, these data show that SKCa and IKCa channels in ECs profoundly modulate PA tone and CBF, whereas BKCa channels in SMCs only modestly influence PA diameter. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1175-1186; doi:10.1038/jcbfm.2010.214; published online 22 December 2010