Endothelial SKCa and IKCa channels regulate brain parenchymal arteriolar diameter and cortical cerebral blood flow

摘要

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 (∼154 pA/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-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 IK_Ca channels in ECs profoundly modulate PA tone and CBF, whereas BK_Ca channels in SMCs only modestly influence PA diameter.