Division of Neurosciences, Institute of Cell Physiology, National Autonomous University of Mexico, Circuito Exterior S/N, Ciudad Universitaria, 04510 Mexico City, Mexico.
Neuroscience. 2010 May 5;167(2):298-311. doi: 10.1016/j.neuroscience.2010.01.046. Epub 2010 Feb 6.
Recent evidence suggests a major role for ionic fluxes in apoptotic cell death and apoptotic volume decrease. Cerebellar granule neurons (CGN) undergo apoptosis when they are treated with staurosporine or camptothecin (CPT) or when cells are transferred from high extracellular potassium (25 mM KCl K(+), K25) to low potassium concentration (5 mM KCl K(+), K5). In this study we described that all three apoptotic conditions induced apoptotic volume decrease in CGN and that two different potassium channel blockers, cesium (Cs(+)) and tetraethylammonium (TEA(+)), prevented the apoptotic volume decrease, caspase-3 activation, nuclear condensation and cell death induced by K5 and CPT, but not by staurosporine. Cs(+) and TEA(+) also blocked membrane currents generated in K5 conditions in CGN. On the other hand, non specific Cl(-) channel blockers such as 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS) prevented loss of cell volume induced by K5 or staurosporine. Only the Cl(-) channels blocker but not the K(+) channels blockers protected from staurosporine-induced death of CGN. These data suggest that ionic fluxes play a key role in the activation of the apoptotic volume decrease and apoptotic death of CGN, but the fine mechanism seems to depend on the apoptotic condition.
最近的证据表明，离子流在细胞凋亡和凋亡体积减少中起着重要作用。小脑颗粒神经元（CGN）在使用星形孢菌素或喜树碱（CPT）处理或从高细胞外钾（25mM KCl[K+]（e），K25）转移到低钾浓度（5mM KCl[K+]（e），K5）时会发生凋亡。在这项研究中，我们描述了所有三种凋亡条件都会诱导 CGN 的凋亡体积减少，并且两种不同的钾通道阻断剂，铯（Cs+）和四乙铵（TEA+），可以防止由 K5 和 CPT 诱导的凋亡体积减少、半胱天冬酶-3 激活、核浓缩和细胞死亡，但不能防止由星形孢菌素诱导的凋亡体积减少、半胱天冬酶-3 激活、核浓缩和细胞死亡。Cs+和 TEA+还阻断了 CGN 在 K5 条件下产生的膜电流。另一方面，非特异性 Cl-通道阻断剂，如 4,4'-二异硫氰基-二苯乙烯-2,2'-二磺酸（DIDS），可以防止 K5 或星形孢菌素诱导的细胞体积减少。只有 Cl-通道阻断剂而不是 K+通道阻断剂可以防止 CGN 因星形孢菌素诱导的死亡。这些数据表明，离子流在 CGN 的凋亡体积减少和凋亡死亡的激活中起着关键作用，但精细的机制似乎取决于凋亡条件。
