Voltage-dependent amplification of synaptic inputs in respiratory motoneurones
Voltage-dependent amplification of synaptic inputs in respiratory motoneurones
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DOI：
10.1113/jphysiol.2011.225789
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发表时间：
2012-07-01
影响因子：
5.5
通讯作者：
Kirkwood, P. A.
中科院分区：
文献类型：
--
作者：
Denton, M. Enriquez;Wienecke, J.;Kirkwood, P. A.
关键点在自然发生的运动动作中，各种兴奋性和抑制性输入整合到脊髓运动神经元的过程还不是很清楚，主要是因为运动神经元内有放大机制，可以控制输入的有效强度。对这些过程的了解对于理解运动神经元疾病或脊髓损伤或中风呼吸后的痉挛是一种在实验条件下正常持续的自然运动行为非常重要，本研究首次研究了呼吸运动神经元可能的放大过程。在控制最重要的呼吸肌--横隔肌的膈运动神经元中，我们发现，其他运动神经元中最受欢迎的机制--通过钙通道激活持续的内向电流--似乎起到了很小的作用。相反，突触电流的调制(通过NMDA通道)似乎更重要。本文研究了持续内向电流(PIC)在猫呼吸运动神经元(膈吸气和胸呼气)中的作用。使用去大脑、未麻醉或巴比妥钠麻醉的制剂。在呼气运动神经元中，去大脑动物可观察到平台电位，但在麻醉状态下观察不到平台电位。对于膈运动神经元，在两种状态下都没有观察到平台电位(除了一个运动神经元在通过延髓损毁的方式取消呼吸驱动后)，但所有的运动神经元都显示出CRDPs的电压依赖性放大，在很大的膜电位范围内，太宽而不主要是PIC激活的结果。扩增的测量被限制在激发阶段，因此排除了抑制阶段。在阻力最低的运动神经元中，最小CRDP的扩增作用最大，在细胞内注射NMDA通道阻滞剂MK-801后，扩增作用减弱或消失。在相同的(去大脑的)准备中，非膈神经颈运动神经元很容易诱发出平台电位。我们认为，尽管膈运动神经元对CaV1.3通道有强烈的免疫组织化学标记，但其突触兴奋的电压依赖性放大主要是NMDA通道调制的结果，而不是激活钙通道介导的PIC的结果。不同运动神经元中PIC的不同激活均为CaV1.3阳性，这使我们推测PIC的下行调制比迄今所认为的更具选择性。
Key points The processes whereby various excitatory and inhibitory inputs are integrated in spinal motoneurones during naturally occurring motor acts are not well understood, largely because there are amplifying mechanisms within the motoneurone that can control the effective strengths of the inputs. Knowledge of these processes is important in understanding conditions such as motoneurone disease, or the spasticity that can follow spinal cord injury or stroke Respiration is a natural motor act that continues normally under experimental conditions, and this study investigated, for the first time, the likely amplifying processes at work in respiratory motoneurones. In phrenic motoneurones, which control the most important respiratory muscle, the diaphragm, we found that the mechanism most favoured by investigations in other motoneurones, the activation of persistent inward currents via calcium channels, appears to make a very small contribution. Instead, modulation of synaptic currents (through NMDA channels) appears to be more important. Abstract The role of persistent inward currents (PICs) in cat respiratory motoneurones (phrenic inspiratory and thoracic expiratory) was investigated by studying the voltage-dependent amplification of central respiratory drive potentials (CRDPs), recorded intracellularly, with action potentials blocked with the local anaesthetic derivative, QX-314. Decerebrate unanaesthetized or barbiturate-anaesthetized preparations were used. In expiratory motoneurones, plateau potentials were observed in the decerebrates, but not under anaesthesia. For phrenic motoneurones, no plateau potentials were observed in either state (except in one motoneurone after the abolition of the respiratory drive by means of a medullary lesion), but all motoneurones showed voltage-dependent amplification of the CRDPs, over a wide range of membrane potentials, too wide to result mainly from PIC activation. The measurements of the amplification were restricted to the phase of excitation, thus excluding the inhibitory phase. Amplification was found to be greatest for the smallest CRDPs in the lowest resistance motoneurones and was reduced or abolished following intracellular injection of the NMDA channel blocker, MK-801. Plateau potentials were readily evoked in non-phrenic cervical motoneurones in the same (decerebrate) preparations. We conclude that the voltage-dependent amplification of synaptic excitation in phrenic motoneurones is mainly the result of NMDA channel modulation rather than the activation of Ca2+ channel mediated PICs, despite phrenic motoneurones being strongly immunohistochemically labelled for CaV1.3 channels. The differential PIC activation in different motoneurones, all of which are CaV1.3 positive, leads us to postulate that the descending modulation of PICs is more selective than has hitherto been believed.