Dentate gyrus granule cells acutely dissociated from hippocampal slices obtained from chronic temporal lobe epilepsy (TLE) patients displayed a high-voltage activated (HVA) Ca2+ conductance with a pronounced Ca2+-dependent inactivation. 2. Inactivation time constants and peak HVA Ca2+ current (ICa) amplitudes did not differ between perforated patch and whole-cell recordings without added exogenous Ca2+ buffers, indicating that the Ca2+-dependent characteristics of ICa inactivation were well preserved in whole-cell recordings. 3. Inactivation time constants correlated with whole-cell ICa, and were increased when Ca2+ was replaced with Ba2+ in the external solution or 5 mM BAPTA was added to the pipette solution. 4. In recordings without added exogenous Ca2+ buffers, the time course of ICa inactivation was comparable between human TLE and kindled rat granule cells. Conversely, the time course of ICa in human TLE granule cells loaded with 5 mM intracellular BAPTA resembled that observed in buffer-free recordings from control rat neurones. 5. The loss of a putative intraneuronal Ca2+ buffer, the Ca2+-binding protein calbindin (CB), from human granule cells during TLE may result in the pronounced Ca2+-dependent ICa inactivation. This process could serve a neuroprotective role by significantly decreasing Ca2+ entry during prolonged trains of action potentials known to occur during seizures.
摘要
从慢性颞叶癫痫（TLE）患者获得的海马切片中急性分离出的齿状回颗粒细胞表现出高电压激活（HVA）Ca2+电导，并伴有明显的Ca2+依赖性失活。2. 在不添加外源Ca2+缓冲剂的穿孔膜片钳和全细胞记录中，失活时间常数和HVA Ca2+电流（ICa）峰值幅度没有差异，这表明在全细胞记录中ICa失活的Ca2+依赖性特征得到了很好的保留。3. 失活时间常数与全细胞ICa相关，当外部溶液中的Ca2+被Ba2+取代或向移液管溶液中添加5 mM BAPTA时，失活时间常数增加。4. 在不添加外源Ca2+缓冲剂的记录中，人类TLE和点燃大鼠颗粒细胞之间ICa失活的时间进程相当。相反，加载5 mM细胞内BAPTA的人类TLE颗粒细胞中ICa的时间进程类似于从对照大鼠神经元的无缓冲记录中观察到的情况。5. 在TLE期间，人类颗粒细胞中假定的神经元内Ca2+缓冲剂、Ca2+结合蛋白钙结合蛋白（CB）的丧失可能导致明显的Ca2+依赖性ICa失活。这一过程可能通过在癫痫发作期间已知发生的长时间动作电位序列中显著减少Ca2+内流而起到神经保护作用。
