Beck H, Steffens R, Heinemann U, Elger C E
Department of Epileptology, University of Bonn Medical Center, Germany.
J Neurophysiol. 1997 Mar;77(3):1526-37. doi: 10.1152/jn.1997.77.3.1526.
Properties of Ba2+ currents through voltage-dependent Ca2+ channels (IBa) were investigated in 61 dentate granule cells acutely isolated from the resected hippocampus of nine patients with therapy-refractory temporal lobe epilepsy (TLE). Currents with a high threshold of activation (HVA) peaked at 0 mV, and showed some time-dependent inactivation and a voltage of half-maximal steady-state inactivation (V1/2inact) of -16.4 mV. Application of saturating doses of omega-conotoxin (omega-CgTx) GVIA or nifedipine distinguished characteristic N-type (38%) and L-type (62% of HVA currents) Ca2+ currents. Combined application of both agents blocked HVA currents by > 95%. In a 10-mo-old child but not in adult patients, an omega-agatoxin IVA (omega-AgaTxIVA)-sensitive but omega-CgTx MVIIC-insensitive, noninactivating component of HVA currents (approximately 24%) was present that most probably corresponds to a P-type current. A T-type Ca2+ current could be separated from HVA components on the basis of its steady-state voltage-dependent inactivation (V1/2inact = -71.0 mV). The T-type Ca2+ current isolated by subtraction peaked at more negative potentials (-10 mV), showed a significantly more rapid time-dependent inactivation, and could be selectively blocked by low concentrations of Ni2+. It was insensitive to nifedipine and omega-CgTx GVIA. We conclude that L-, N-, and T-type currents are present in adult human dentate granule cells and an additional P-type current is present in neurons from a 10-mo-old patient. These data may provide a basis for comparison with animal models of epilepsy and for the elucidation of mechanisms of action of drugs intended for use in human disease.
在从9例难治性颞叶癫痫（TLE）患者切除的海马中急性分离出的61个齿状颗粒细胞中，研究了通过电压依赖性钙通道（IBa）的Ba2+电流特性。具有高激活阈值（HVA）的电流在0 mV时达到峰值，表现出一些时间依赖性失活，半最大稳态失活电压（V1/2inact）为-16.4 mV。应用饱和剂量的ω-芋螺毒素（ω-CgTx）GVIA或硝苯地平可区分特征性的N型（38%）和L型（HVA电流的62%）钙电流。两种药物联合应用可使HVA电流阻断>95%。在一名10个月大的儿童而非成年患者中，存在一种HVA电流的ω-阿加毒素IVA（ω-AgaTxIVA）敏感但ω-CgTx MVIIC不敏感的非失活成分（约24%），很可能对应于P型电流。T型钙电流可根据其稳态电压依赖性失活（V1/2inact = -71.0 mV）与HVA成分分离。通过减法分离出的T型钙电流在更负的电位（-10 mV）时达到峰值，表现出明显更快的时间依赖性失活，并且可被低浓度的Ni2+选择性阻断。它对硝苯地平和ω-CgTx GVIA不敏感。我们得出结论，L型、N型和T型电流存在于成年人类齿状颗粒细胞中，一名10个月大患者的神经元中还存在额外的P型电流。这些数据可能为与癫痫动物模型进行比较以及阐明用于人类疾病的药物作用机制提供基础。
