Pappas C A, Ullrich N, Sontheimer H
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Neuroreport. 1994 Dec 30;6(1):193-6. doi: 10.1097/00001756-199412300-00049.
Astrocyte proliferation was studied in primary cultures of rat spinal cord by [3H]thymidine uptake and was significantly reduced by culturing cells for 24 h in the presence of agents known to block astrocytic K+ channels: Cs+, Ba2+, 4-AP and tetraethylammonium (TEA). To determine whether effects were mediated by changes in Vm or pHi, these parameters were studied electrophysiologically or ratiometrically, using BCECF. Of the four K+ channel blockers, only Ba2+ depolarized astrocytes significantly. However, all four K+ channel blockers resulted in an alkaline shift in pHi. Under culture conditions that altered pHi in a defined way, proliferation strongly depended on pHi, with highest rates at pH approximately 6.7 and growth inhibition at more acidic or alkaline conditions. These observations suggest that astrocyte proliferation is sensitive to changes in pHi and that K+ channel blockers may exhibit their antiproliferative effects through changes in pHi.
通过[3H]胸苷摄取研究了大鼠脊髓原代培养物中的星形胶质细胞增殖，并且在已知可阻断星形胶质细胞钾离子通道的试剂存在下将细胞培养24小时后，星形胶质细胞增殖显著降低，这些试剂包括：铯离子（Cs+）、钡离子（Ba2+）、4-氨基吡啶（4-AP）和四乙铵（TEA）。为了确定这些作用是否由膜电位（Vm）或细胞内pH值（pHi）的变化介导，使用BCECF通过电生理学或比率测定法研究了这些参数。在四种钾离子通道阻滞剂中，只有Ba2+能使星形胶质细胞显著去极化。然而，所有四种钾离子通道阻滞剂都导致pHi发生碱化偏移。在以特定方式改变pHi的培养条件下，增殖强烈依赖于pHi，在pH约为6.7时增殖速率最高，在更酸性或碱性条件下生长受到抑制。这些观察结果表明，星形胶质细胞增殖对pHi的变化敏感，并且钾离子通道阻滞剂可能通过pHi的变化发挥其抗增殖作用。
