Schwarzacher S W, Pestean A, Günther S, Ballanyi K
Zentrum Anatomie, Universität Göttingen, Kreuzbergring 36, D-37075, Göttingen, Germany.
Neuroscience. 2002;115(4):1247-59. doi: 10.1016/s0306-4522(02)00540-7.
Respiration-related membrane potential fluctuations were recorded in hypoglossal (XII) motoneurons and pre-Bötzinger complex (pre-BötC) interneurons in medullary slices from perinatal rats. Bath application of serotonin (5-HT) evoked a ketanserine-sensitive depolarization (approximately 11 mV) and tonic spike discharge in XII motoneurons, whereas pre-BötC neurons responded with a <6 mV depolarization and no tonic discharge. The membrane effects were accompanied by an increase in respiratory frequency by up to 260% in 64% of preparations. A frequency decrease leading to block of respiratory activity could also occur (20%) as well as an initial acceleration that turned into a frequency depression (16%). In contrast, iontophoresis of 5-HT into the pre-BötC exclusively increased respiratory frequency by 30-220%, whereas iontophoresis into the XII nucleus did not change respiratory frequency but induced tonic nerve discharge. The effects of local iontophoretic administration of 5-HT on membrane properties of XII and pre-BötC cells were very similar to those upon bath application. Bath application and iontophoresis of the 5-HT2 receptor agonist -methyl-hydroxytryptamine mimicked the effects of 5-HT. Bath application of the 5-HT1A receptor agonist 8-hydroxydipropylaminotetralin hydrobromide did not affect XII nerve bursting or pre-BötC neurons. Iontophoresis of 8-hydroxydipropylaminotetralin hydrobromide had almost no effect on respiratory frequency and induced in the interneurons either a depolarization or hyperpolarization (<5 mV) which was blocked by the 5-HT1A receptor antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)N-2-pyridinylcyclohexane carboxamide. In conclusion, 5-HT-evoked tonic excitation of respiratory XII motoneurons is mediated by postsynaptic 5-HT2 receptors. The excitatory effects on respiratory rhythm are also primarily attributable to postsynaptic 5-HT2 receptors of pre-BötC neurons. Additional modulatory effects on the interneurons appear to be mediated by postsynaptic 5-HT1A receptors.
在围产期大鼠延髓切片的舌下神经（XII）运动神经元和前包钦格复合体（pre - BötC）中间神经元中记录与呼吸相关的膜电位波动。浴加血清素（5 - HT）可诱发舌下神经运动神经元出现酮色林敏感的去极化（约11 mV）和强直性放电，而前包钦格复合体神经元的反应是去极化小于6 mV且无强直性放电。这些膜效应伴随着64%的标本中呼吸频率增加高达260%。也可能出现导致呼吸活动阻滞的频率降低（20%）以及最初加速随后转变为频率抑制的情况（16%）。相比之下，将5 - HT离子导入前包钦格复合体仅使呼吸频率增加30 - 220%，而将其离子导入舌下神经核不会改变呼吸频率，但会诱发强直性神经放电。局部离子导入5 - HT对舌下神经和前包钦格复合体细胞的膜特性的影响与浴加给药时非常相似。5 - HT2受体激动剂 - 甲基 - 羟基色胺的浴加给药和离子导入模拟了5 - HT的作用。5 - HT1A受体激动剂氢溴酸8 - 羟基二丙基氨基四氢萘的浴加给药不影响舌下神经的爆发活动或前包钦格复合体神经元。氢溴酸8 - 羟基二丙基氨基四氢萘的离子导入对呼吸频率几乎没有影响，并在中间神经元中诱发去极化或超极化（<5 mV），这被5 - HT1A受体拮抗剂N - （2 - （4 - （2 - 甲氧基苯基） - 1 - 哌嗪基）乙基）N - 2 - 吡啶基环己烷甲酰胺所阻断。总之，5 - HT诱发的呼吸舌下神经运动神经元的强直性兴奋是由突触后5 - HT2受体介导的。对呼吸节律的兴奋作用也主要归因于前包钦格复合体神经元的突触后5 - HT2受体。对中间神经元的额外调节作用似乎是由突触后5 - HT1A受体介导的。
