Watanabe Shigeo, Hong Min, Lasser-Ross Nechama, Ross William N
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
J Physiol. 2006 Sep 1;575(Pt 2):455-68. doi: 10.1113/jphysiol.2006.114231. Epub 2006 Jun 29.
Repetitive synaptic stimulation in the stratum radiatum (SR) evokes large amplitude Ca2+ waves in the thick apical dendrites of hippocampal CA1 pyramidal neurons. These waves are initiated by activation of metabotropic glutamate receptors (mGluRs), which mobilize inositol-1,4,5-trisphospate (IP3) and release Ca2+ from intracellular stores. We explored mechanisms that modulate the spatial properties of these waves. Higher stimulus current evoked waves of increasing spatial extent. Most waves did not propagate through the soma; the majority stopped close to the junction of the soma and apical dendrite. Pairing strong stimulation with one electrode and subthreshold stimulation with another (associative activation) extended the waves distally but failed to extend waves into the cell body. Pairing synaptic stimulation with backpropagating action potentials enhanced the likelihood of wave generation but did not extend the waves to the somatic region. Priming the stores with Ca2+ entry through voltage dependent channels modulated wave properties but did not extend them past the dendrites. These results are consistent with propagation failing due to the dilution of synaptically generated IP3 as it diffuses into the large volume of the soma (impedance mismatch). Synaptically activating waves in the presence of low concentrations of carbachol, which probably increased the tonic level of IP3 throughout the cell, enhanced the extent of propagation and generated waves that invaded the soma, as long as low-affinity indicators were used to detect the [Ca2+]i changes. Consistent with this explanation direct injection of IP3 into the soma promoted wave propagation into this region. Ca2+ waves that propagated through the cell body were interesting because they did not fill the volume of the soma, but passed through the centre, often with large amplitude. These waves may be particularly effective in activating gene expression and protein synthesis.
在海马体CA1锥体神经元的厚顶树突中，辐射层（SR）的重复性突触刺激会诱发大幅度的Ca2+波。这些波由代谢型谷氨酸受体（mGluRs）激活引发，mGluRs会动员肌醇-1,4,5-三磷酸（IP3）并从细胞内储存中释放Ca2+。我们探究了调节这些波空间特性的机制。更高的刺激电流会诱发空间范围不断扩大的波。大多数波不会通过胞体传播；大多数在靠近胞体和顶树突的交界处就停止了。将一个电极的强刺激与另一个电极的阈下刺激配对（联合激活）会使波向远端扩展，但无法将波扩展到细胞体。将突触刺激与反向传播动作电位配对会增加波产生的可能性，但不会将波扩展到体细胞区域。通过电压依赖性通道使Ca2+进入来预处理储存会调节波的特性，但不会使它们延伸到树突之外。这些结果与由于突触产生的IP3扩散到大量的胞体中而稀释（阻抗不匹配）导致传播失败是一致的。在低浓度卡巴胆碱存在的情况下突触激活波，这可能会增加整个细胞中IP3的静息水平，增强了传播范围并产生了侵入胞体的波，只要使用低亲和力指示剂来检测[Ca2+]i变化。与这种解释一致，直接向胞体注射IP3会促进波传播到该区域。通过细胞体传播的Ca2+波很有趣，因为它们没有充满胞体的体积，而是穿过中心，通常幅度很大。这些波可能在激活基因表达和蛋白质合成方面特别有效。
