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 (SK Ca) and intermediate-conductance (IKCa) KCa channels and large-conductance KCa (BKCa) channels in endothelial cells (ECs) and smooth muscle cells (SMCs) of PAs. Both SK Ca 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 (154 pA/pF), but were undetectable in PA ECs. Pressurized PAs constricted to inhibition of SK Ca (16%) and IKCa (16%) channels, but were only modestly affected by inhibition of BKCa channels (5%). Blockade of SK Ca and IKCa channels decreased resting cortical cerebral blood flow (CBF) by 15%. NS309 (6,7-dichloro-1H-indole-2,3-dione3-oxime), a SKCa /IKCa 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 IKCa channels in ECs profoundly modulate PA tone and CBF, whereas BKCa channels in SMCs only modestly influence PA diameter. © 2011 ISCBFM All rights reserved.