Department of Pharmacology, College of Medicine, University of Vermont, Burlington, VT 05405-0068, USA.
J Cereb Blood Flow Metab. 2011 May;31(5):1175-86. doi: 10.1038/jcbfm.2010.214. Epub 2010 Dec 22.
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 (154 pA/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.
钙敏钾 (K(Ca)) 通道已被证明可调节脑软脑膜动脉的直径；然而，对于其在控制脑实质小动脉 (PA) 中的作用知之甚少。我们研究了小电导 (SK(Ca)) 和中电导 (IK(Ca)) K(Ca) 通道以及大电导 K(Ca) (BK(Ca)) 通道在 PA 内皮细胞 (EC) 和平滑肌细胞 (SMC) 中的功能和细胞分布。在分离的 PA EC 中，SK(Ca) 和 IK(Ca) 通道均传导外向电流（+40 mV 时的电流密度分别约为 20 pA/pF 和 28 pA/pF），但在 PA SMC 中未检测到这些电流。相比之下，BK(Ca) 电流在 PA SMC 中很明显（154 pA/pF），但在 PA EC 中无法检测到。加压 PA 对 SK(Ca) (16%) 和 IK(Ca) (16%) 通道的抑制作用收缩，但对 BK(Ca) 通道的抑制作用 (5%) 仅有适度影响。SK(Ca) 和 IK(Ca) 通道的阻断使皮质脑血流 (CBF) 减少约 15%。NS309（6,7-二氯-1H-吲哚-2,3-二酮 3-肟），一种 SK(Ca)/IK(Ca) 通道开放剂，可使 PA SMC 最大超极化约 27 mV，最大程度扩张加压 PA，并使 CBF 增加约 40%。总之，这些数据表明，EC 中的 SK(Ca) 和 IK(Ca) 通道可显著调节 PA 张力和 CBF，而 SMC 中的 BK(Ca) 通道仅适度影响 PA 直径。
