Computational estimation of the distribution of L-type Ca2+ channels in motoneurons based on variable threshold of activation of persistent inward currents
Computational estimation of the distribution of L-type Ca2+ channels in motoneurons based on variable threshold of activation of persistent inward currents
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DOI：
10.1152/jn.00646.2005
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发表时间：
2006-01-01
影响因子：
2.5
通讯作者：
Rose, PK
中科院分区：
文献类型：
--
作者：
Bui, TV;Ter-Mikaelian, M;Rose, PK
在神经调节剂如血清素和去甲肾上腺素存在的情况下，运动神经元表现出持续向内电流（PICs），用于放大突触输入。这些PICs的主要组成部分是由l型Ca2+通道介导的。基于电生理研究的估计表明，这些通道位于树突上，但对其精确分布的免疫组织化学研究产生了不同的结果。我们的目标是使用计算方法确定这些通道的分布。在没有或存在突触活动的情况下，通过体细胞电流注射激活PICs的理论分析表明，l型Ca2+通道可能在树突状树中分离到25-200 μ m长的离散热点，并集中在距离体细胞100-400 μ m的地方。基于对猫颈部运动神经元结构的详细解剖测量的室室模型，这些区域包含l型Ca2+通道，产生由PIC激活引起的平台电位。此外，我们重复了实验观察，PICs被激活的躯体阈值通过抑制性突触的强直激活而去极化，通过兴奋性突触的强直激活而超极化。l型Ca2+通道均匀分布的模型无法复制PIC激活的体细胞阈值变化。因此，我们得出结论，介导平台电位的l型Ca2+通道集仅限于树突树的离散区域。此外，这种分布导致运动神经元的树突树划分为亚单位，这些亚单位的顺序激活导致突触输入的分级放大。
In the presence of neuromodulators such as serotonin and noradrenaline, motoneurons exhibit persistent inward currents (PICs) that serve to amplify synaptic inputs. A major component of these PICs is mediated by L-type Ca2+ channels. Estimates based on electrophysiological studies indicate that these channels are located on the dendrites, but immunohistochemical studies of their precise distribution have yielded different results. Our goal was to determine the distribution of these channels using computational methods. A theoretical analysis of the activation of PICs by a somatic current injection in the absence or presence of synaptic activity suggests that L-type Ca2+ channels may be segregated to discrete hot spots 25-200 mu m long and centered 100-400 mu m from the soma in the dendritic tree. Compartmental models based on detailed anatomical measurements of the structure of feline neck motoneurons with L-type Ca2+ channels incorporated in these regions produced plateau potentials resulting from PIC activation. Furthermore, we replicated the experimental observation that the somatic threshold at which PICs were activated was depolarized by tonic activation of inhibitory synapses and hyperpolarized by tonic activation of excitatory synapses. Models with L-type Ca2+ channels distributed uniformly were unable to replicate the change in somatic threshold of PIC activation. Therefore we conclude that the set of L-type Ca2+ channels mediating plateau potentials is restricted to discrete regions in the dendritic tree. Furthermore, this distribution leads to the compartmentalization of the dendritic tree of motoneurons into subunits whose sequential activation lead to the graded amplification of synaptic inputs.