Tegnér J, Grillner S
Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
J Neurophysiol. 1999 Mar;81(3):1318-29. doi: 10.1152/jn.1999.81.3.1318.
The GABAB-mediated modulation of spinal neurons in the lamprey is investigated in this study. Activation of GABAB receptors reduces calcium currents through both low- (LVA) and high-voltage activated (HVA) calcium channels, which subsequently results in the reduction of the calcium-dependent potassium (KCa) current. This in turn will reduce the peak amplitude of the afterhyperpolarization (AHP). We used the modulatory effects of GABAB receptor activation on N-methyl-D-aspartate (NMDA)-induced, TTX-resistant membrane potential oscillations as an experimental model in which to separate the effects of GABAB receptor activation on LVA calcium channels from that on KCa channels. We show experimentally and by using simulations that a direct effect on LVA calcium channels can account for the effects of GABAB receptor activation on intrinsic membrane potential oscillations to a larger extent than indirect effects mediated via KCa channels. Furthermore, by conducting experiments and simulations on intrinsic membrane potential oscillations, we find that KCa channels may be activated by calcium entering through LVA calcium channels, providing that the decay kinetics of the calcium that enters through LVA calcium channels is not as slow as the calcium entering via NMDA receptors. A combined experimental and computational analysis revealed that the LVA calcium current also contributes to neuronal firing properties.
本研究对七鳃鳗中GABAB介导的脊髓神经元调节作用进行了研究。GABAB受体的激活会降低通过低电压激活（LVA）和高电压激活（HVA）钙通道的钙电流，进而导致钙依赖性钾电流（KCa）降低。这反过来又会降低超极化后电位（AHP）的峰值幅度。我们利用GABAB受体激活对N-甲基-D-天冬氨酸（NMDA）诱导的、对河豚毒素（TTX）不敏感的膜电位振荡的调节作用作为实验模型，以区分GABAB受体激活对LVA钙通道和对KCa通道的影响。我们通过实验和模拟表明，对LVA钙通道的直接作用比通过KCa通道介导的间接作用在更大程度上解释了GABAB受体激活对固有膜电位振荡的影响。此外，通过对固有膜电位振荡进行实验和模拟，我们发现KCa通道可能被通过LVA钙通道进入的钙激活，前提是通过LVA钙通道进入的钙的衰减动力学不像通过NMDA受体进入的钙那样缓慢。综合实验和计算分析表明，LVA钙电流也对神经元的放电特性有贡献。
