Sakagami K, Kawamura H, Wu D M, Puro D G
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105, USA.
Microvasc Res. 2001 Sep;62(2):196-203. doi: 10.1006/mvre.2001.2343.
In the CNS, contractile pericytes positioned on endothelium-lined lumens appear to play a role in regulating capillary blood flow. This function may be particularly important in the retina where pericytes are more numerous than in other tissues. Despite the importance of pericytes, knowledge of the effects of vasoactive molecules, such as nitric oxide (NO), on the physiology of these cells is limited. Since it is likely that ion channels play a role in the response of pericytes to signaling molecules from other cells, we used the perforated-patch configuration of the patch-clamp technique to record the whole-cell currents of pericytes located on microvessels freshly isolated from the rat retina. We found that voltage-gated calcium currents and calcium-activated chloride currents were inhibited during exposure to the NO donor, sodium nitroprusside (SNP). 8-Bromo-cyclic guanosine monophosphate (cGMP) mimicked these effects. In contrast, neither SNP nor the cGMP analog significantly affected the potassium or nonspecific cation conductances, which establish the resting membrane potential of retinal pericytes. Consistent with endogenous NO suppressing pericyte channel activity, exposure of isolated microvessels to an inhibitor of NO synthase increased the calcium and chloride currents. Since our experiments indicate that chloride channel activity is dependent, in part, upon the function of voltage-gated calcium channels, we postulate that a NO/cGMP-mediated inhibition of calcium channels reduces calcium influx and, thereby, lessens the opening of the calcium-activated chloride channels. This may be one mechanism by which NO decreases the contractile tone of pericytes.
在中枢神经系统中，位于内皮衬里管腔上的收缩性周细胞似乎在调节毛细血管血流中发挥作用。这种功能在视网膜中可能尤为重要，因为视网膜中的周细胞比其他组织中的更多。尽管周细胞很重要，但关于血管活性分子（如一氧化氮（NO））对这些细胞生理作用的了解仍然有限。由于离子通道可能在周细胞对来自其他细胞的信号分子的反应中起作用，我们使用膜片钳技术的穿孔膜片配置来记录从大鼠视网膜新鲜分离的微血管上周细胞的全细胞电流。我们发现，在暴露于NO供体硝普钠（SNP）期间，电压门控钙电流和钙激活氯电流受到抑制。8-溴环鸟苷单磷酸（cGMP）模拟了这些作用。相反，SNP和cGMP类似物均未显著影响建立视网膜周细胞静息膜电位的钾或非特异性阳离子电导。与内源性NO抑制周细胞通道活性一致，将分离的微血管暴露于NO合酶抑制剂会增加钙电流和氯电流。由于我们的实验表明氯通道活性部分依赖于电压门控钙通道的功能，我们推测NO/cGMP介导的钙通道抑制会减少钙内流，从而减少钙激活氯通道的开放。这可能是NO降低周细胞收缩张力的一种机制。
