Caro Anton, Tarabova Bohumila, Rojo-Ruiz Jonathan, Lacinova Lubica
Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Gen Physiol Biophys. 2011;30 Spec No:S44-53. doi: 10.4149/gpb_2011_SI1_44.
L-type calcium channels (LTCC) are important functional elements of hippocampal neurons contributing to processes like memory formation and gene expression. Mice lacking the Ca(V)1.2 channel in hippocampal pyramidal cells exhibited defects in spatial memory (Moosmang et al. 2005) and lowered frequency of repetitive action potential (AP) firing (Lacinova et al. 2008). We tested the contribution of LTCC to AP firing of cultured rat neonatal hippocampal neurons using the dihydropyridine channel blocker nimodipine. Ionic currents and APs were recorded in the whole cell patch clamp configuration. A prolonged depolarizing current pulse activated the firing of a series of APs. The presence of 10 μM nimodipine blocked all but the first AP in series. This concentration, which is potent enough to completely block LTCC, inhibited about 35-50% of the total calcium current. In addition, nimodipine blocked about 50% of both calcium-dependent and voltage-dependent potassium currents whereas the sodium current was not affected. We suggest that nimodipine suppressed the firing of APs in cultured neonatal rat hippocampal neurons due to inhibition of both calcium and potassium currents.
L型钙通道（LTCC）是海马神经元的重要功能元件，参与记忆形成和基因表达等过程。海马锥体细胞中缺乏Ca(V)1.2通道的小鼠表现出空间记忆缺陷（Moosmang等人，2005年）和重复动作电位（AP）发放频率降低（Lacinova等人，2008年）。我们使用二氢吡啶通道阻滞剂尼莫地平测试了LTCC对培养的新生大鼠海马神经元AP发放的贡献。在全细胞膜片钳配置下记录离子电流和AP。一个延长的去极化电流脉冲激活了一系列AP的发放。10μM尼莫地平的存在阻断了除第一个AP之外的所有串联AP。这个浓度足以完全阻断LTCC，抑制了约35 - 50%的总钙电流。此外，尼莫地平阻断了约50%的钙依赖性和电压依赖性钾电流，而钠电流不受影响。我们认为尼莫地平抑制了培养的新生大鼠海马神经元中AP的发放，这是由于抑制了钙电流和钾电流。
