Institut of Neurosciences, Department Cell Biology, Physiology and Immunology and Centro de Investigación en Red sobre Enfermedades Neurodegenerativas, Universitat Autonoma de Barcelona, Spain.
J Neurophysiol. 2010 Mar;103(3):1295-303. doi: 10.1152/jn.00734.2009. Epub 2010 Jan 6.
Recruitment and repetitive firing of spinal motoneurons depend on the activation of persistent inward calcium and sodium currents (PICs) that are in turn facilitated by serotonin and norepinephrine that arise primarily from the brain stem. Considering that in rats motoneuron PICs are greatly facilitated by increasing the presynaptic release of norepinephrine with amphetamine, we sought similar evidence for the modulation of PICs in human motoneurons. Pairs of motor units were recorded during a gradually increasing and then decreasing voluntary contraction. The firing frequency (F) of the lower-threshold (control) motor unit was used as an estimate of the synaptic input to the higher-threshold (test) motor unit. Generally, PICs are initiated during the recruitment of a motoneuron and subsequently provide a fixed depolarizing current that helps the synaptic input maintain firing until derecruitment. Thus the amplitude of the PIC in the test motor unit was estimated from the difference in synaptic input (DeltaF) needed to maintain minimal firing once the PIC was fully activated (measured at the time of test unit derecruitment) compared with the larger synaptic input required to initiate firing prior to full PIC activation (measured at the time of test unit recruitment; DeltaF = F(recruit) - F(derecruit)). Moreover, the activation time of the PIC was estimated as the minimal contraction duration needed to produce a maximal PIC (DeltaF). In five subjects, oral administration of amphetamine, but not placebo, increased the DeltaF by 62% [from 3.7 +/- 0.6 to 6.0 +/- 0.8 (SD) imp/s, P = 0.001] and decreased the time needed to activate a maximal DeltaF from approximately 2 to 0.5 s. Both findings suggest that the endogenous facilitation of PICs from brain stem derived norepinephrine plays an important role in modulating human motoneuron excitability, readying motoneurons for rapid and sustained activity during periods of high arousal such as stress or fear.
脊髓运动神经元的募集和重复放电依赖于持续内向钙和钠电流（PICs）的激活，而这些电流反过来又受到主要来自脑干的 5-羟色胺和去甲肾上腺素的促进。考虑到在大鼠中，PIC 可以通过增加安非他命引起的去甲肾上腺素的突触前释放而大大促进，我们寻找了类似的证据来证明人类运动神经元 PIC 的调节。在逐渐增加和减少自愿收缩期间记录了一对运动单位。下阈值（对照）运动单位的放电频率（F）被用作对高阈值（测试）运动单位的突触输入的估计。通常，PIC 在运动神经元的募集过程中开始，随后提供固定的去极化电流，有助于突触输入维持放电，直到去募集。因此，测试运动单位中的 PIC 幅度是从维持最小放电所需的突触输入（DeltaF）中估计出来的，一旦 PIC 完全激活（在测试单元去募集时测量），与在完全激活 PIC 之前启动放电所需的较大突触输入（在测试单元募集时测量；DeltaF = F（recruit）- F（derecruit））相比。此外，PIC 的激活时间估计为产生最大 PIC（DeltaF）所需的最小收缩持续时间。在五名受试者中，口服安非他命而非安慰剂使 DeltaF 增加了 62%[从 3.7 +/- 0.6 增加到 6.0 +/- 0.8（SD）imp/s，P = 0.001]，并将激活最大 DeltaF 所需的时间从大约 2 秒减少到 0.5 秒。这两个发现都表明，源自脑干的去甲肾上腺素对内源性促进 PIC 发挥了重要作用，使运动神经元为高唤醒期（如压力或恐惧）的快速和持续活动做好准备。
