Price Diana L, Ludwig Jeffrey W, Mi Huaiyu, Schwarz Thomas L, Ellisman Mark H
Department of Neurosciences and National Center for Microscopy and Imaging Research, University of California, 9500 Gilman Drive, Basic Sciences Building, Suite 1000, San Diego, CA 92093-0608, USA.
Brain Res. 2002 Nov 29;956(2):183-93. doi: 10.1016/s0006-8993(02)03266-3.
Evidence that Ca(2+)-activated K(+) (K(Ca)) channels play a role in cell volume changes and K(+) homeostasis led to a prediction that astrocytes would have K(Ca) channels near blood vessels in order to maintain K(+) homeostasis. Consistent with this thinking the present study demonstrates that rSlo K(Ca) channels are in glial cells of the adult rat central nervous system (CNS) and highly localized to specializations of astrocytes associated with the brain vasculature. Using confocal and thin-section electron microscopic immunolabeling methods the distribution of rSlo was examined in adult rat brain. Strong rSlo immunolabeling was present around the vasculature of most brain regions. Examination of dye-filled hippocampal astrocytes revealed rSlo immunolabeling polarized in astrocytic endfeet. Ultrastructural analysis confirmed that the rSlo staining was concentrated in astrocytic endfeet ensheathing capillaries as well as abutting the pia mater. Immunostaining within the endfeet was predominantly distributed at the plasma membrane directly adjacent to either the vascular basal lamina or the pial surface. The distribution of the aquaporin-4 (AQP-4) water channel was also examined using dye-filled hippocampal astrocytes. In confirmation of earlier reports, intense AQP-4 immunolabeling was generally observed at the perimeter of blood vessels, and coincided with perivascular endfeet and rSlo labeling. We propose that rSlo K(Ca) channels, with their sensitivity to membrane depolarization and intracellular calcium, play a role in the K(+) modulation of cerebral blood flow. Additional knowledge of the molecular and cellular machinery present at perivascular endfeet may provide insight into the structural and functional molecular elements responsible for the neuronal activity-dependent regulation of cerebral blood flow.
钙离子激活钾离子（KCa）通道在细胞体积变化和钾离子稳态中发挥作用的证据，促使人们预测星形胶质细胞在血管附近会有KCa通道，以维持钾离子稳态。与这一观点一致的是，本研究表明，rSlo KCa通道存在于成年大鼠中枢神经系统（CNS）的神经胶质细胞中，并且高度定位于与脑血管系统相关的星形胶质细胞特化部位。使用共聚焦和超薄切片电子显微镜免疫标记方法，在成年大鼠脑中检测了rSlo的分布。在大多数脑区的血管周围都有强烈的rSlo免疫标记。对充满染料的海马星形胶质细胞的检查显示，rSlo免疫标记在星形胶质细胞终足中呈极化分布。超微结构分析证实，rSlo染色集中在包绕毛细血管以及邻接软脑膜的星形胶质细胞终足中。终足内的免疫染色主要分布在直接与血管基膜或软膜表面相邻的质膜上。还使用充满染料的海马星形胶质细胞检查了水通道蛋白4（AQP-4）水通道的分布。正如早期报告所证实的，通常在血管周围观察到强烈的AQP-4免疫标记，并且与血管周围终足和rSlo标记一致。我们提出，rSlo KCa通道因其对膜去极化和细胞内钙的敏感性，在脑血流的钾离子调节中发挥作用。对血管周围终足中存在的分子和细胞机制的更多了解，可能有助于深入了解负责神经元活动依赖性脑血流调节的结构和功能分子元件。
