Substance P-mediated modulation of pacemaker properties in the mammalian respiratory network
Substance P-mediated modulation of pacemaker properties in the mammalian respiratory network
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DOI：
10.1523/jneurosci.1871-04.2004
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发表时间：
2004-08-25
影响因子：
5.3
通讯作者：
Ramirez, JM
中科院分区：
文献类型：
--
作者：
Peña, F;Ramirez, JM
神经调节剂是神经元网络的组成部分，阐明这些物质如何改变神经元活动对于理解网络如何产生模式活动以及最终的行为至关重要。在这项研究中，我们研究了P物质（SP）对小鼠自主活动横切片制备中分离的呼吸网络兴奋作用的细胞机制。SP在所有记录的吸气性起搏器和非起搏器神经元中产生缓慢的去极化。离子交换实验和不同离子通道的阻断剂表明，缓慢的去极化是由低阈值的ttx不敏感阳离子电流激活引起的，该阳离子电流主要携带Na+。sp诱导的慢去极化增加了非起搏器神经元的紧张性放电，并主要增加了Cd2+不敏感起搏器神经元的破裂频率。在Cd2+敏感的起搏器神经元中，爆发频率未受显著影响，而爆发持续时间和振幅比Cd2+不敏感的起搏器神经元增强。在产生nmda依赖性阈下振荡的非起搏器神经元子集中，SP引起动作电位的爆发。我们得出结论，呼吸网络中起搏器活动的程度不是固定的，而是由神经调节剂（如SP）动态调节的。这一发现可能对脑干中SP水平和其他神经调节剂水平下降的Rett综合征具有临床意义。
Neuromodulators are integral parts of a neuronal network, and unraveling how these substances alter neuronal activity is critical for understanding how networks generate patterned activity and, ultimately, behavior. In this study, we examined the cellular mechanisms underlying the excitatory action of substance P (SP) on the respiratory network isolated in spontaneously active transverse slice preparation of mice. SP produced a slow depolarization in all recorded inspiratory pacemaker and non-pacemaker neurons. Ion exchange experiments and blockers for different ion channels suggest that the slow depolarization is caused by the activation of a low-threshold TTX-insensitive cationic current that carries mostly Na+. The SP-induced slow depolarization increased tonic discharge in non-pacemaker neurons and primarily enhanced the frequency of bursting in Cd2+-insensitive pacemaker neurons. In the Cd2+-sensitive pacemaker neuron, the burst frequency was not significantly affected, whereas burst duration and amplitude were more enhanced than in Cd2+-insensitive pacemaker neurons. In a subset of non-pacemaker neurons that produced NMDA-dependent subthreshold oscillations, SP caused the production of bursts of action potentials. We conclude that the degree of pacemaker activity in the respiratory network is not fixed but dynamically regulated by neuromodulators such as SP. This finding may have clinical implications for Rett syndrome in which SP levels along with other neuromodulators are decreased in the brainstem.