Fischer R, Schliess F, Häussinger D
Department of Internal Medicine, Heinrich-Heine-Universität, Düsseldorf, Germany.
Glia. 1997 May;20(1):51-8.
The influence of astrocyte swelling on the cytosolic free calcium concentration [Ca2+]i was studied at the single cell level. Sudden exposure of normo-osmotically (305 mosmol/l) cultured astrocytes to hypo-osmotic medium induced a biphasic increase in cytosolic calcium with an initial peak followed by a sustained plateau. The response was osmolarity dependent and was maximal at 205 mosmol/l with respect to [Ca2+]i and the percentage of responding cells. Other modes of astrocyte swelling [gradual adjustment of hypo-osmolarity, normo-osmotic exposure of hyper-osmotic (405 mosmol/l) maintained cells] produced a much weaker [Ca2+]i response. Change from 405 to 205 mosmol/l, however, resulted in the entire peak and an increased plateau. Experiments with Ca(2+)-free medium and after pretreatment with BAPTA-AM, thapsigargin, phorbol myristate acetate, or nimodipine revealed that the peak mainly resulted from depletion of intracellular Ca2+ stores, whereas the plateau was probably due to capacitative Ca2+ entry and Ca2+ influx independent of store depletion including a nimodipin-sensitive component. Prior depletion of ryanodine-, bradykinin- or ATP-sensitive stores revealed that the initial hypo-osmolarity-induced Ca(2+)-release was from a Ca2+ pool also affected by ATP and bradykinin, but not by ryanodine. The recent finding, that the hypo-osmolarity-induced [Ca2+]i response was completely maintained if phospholipase C-mediated phosphatidylinositol hydrolysis was blocked, suggests that hypo-osmolarity may exert an inositol (1,4,5) triphosphate-independent access to these stores.
在单细胞水平研究了星形胶质细胞肿胀对胞质游离钙浓度[Ca2+]i的影响。将正常渗透压（305 mosmol/l）培养的星形胶质细胞突然暴露于低渗培养基中，可诱导胞质钙双相增加，先是出现一个初始峰值，随后是一个持续的平台期。该反应依赖于渗透压，在205 mosmol/l时，就[Ca2+]i和反应细胞百分比而言达到最大值。星形胶质细胞肿胀的其他模式[低渗的逐渐调节、高渗（405 mosmol/l）维持细胞的正常渗透压暴露]产生的[Ca2+]i反应要弱得多。然而，从405 mosmol/l变为205 mosmol/l会导致整个峰值和升高的平台期。用无钙培养基以及用BAPTA-AM、毒胡萝卜素、佛波醇肉豆蔻酸酯乙酸酯或尼莫地平预处理后的实验表明，峰值主要是由于细胞内Ca2+储存的耗尽，而平台期可能是由于钙池操纵性Ca2+内流和与储存耗尽无关的Ca2+内流，包括一个尼莫地平敏感成分。预先耗尽ryanodine、缓激肽或ATP敏感的储存表明，最初的低渗诱导的Ca(2+)释放来自一个也受ATP和缓激肽影响但不受ryanodine影响的Ca2+池。最近的发现是，如果磷脂酶C介导的磷脂酰肌醇水解被阻断，低渗诱导的[Ca2+]i反应会完全保持，这表明低渗可能通过一种不依赖于肌醇（1,4,5）三磷酸的方式进入这些储存。
