Modulation of hypoglossal motoneuron excitability by NK1 receptor activation in neonatal mice in vitro
Modulation of hypoglossal motoneuron excitability by NK1 receptor activation in neonatal mice in vitro
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NK1受体激活对体外新生小鼠舌下运动神经元兴奋性的调节
DOI：
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
G. Funk
中科院分区：
文献类型：
--
作者：
Kouichi Yasuda;D. M. Robinson;S. Selvaratnam;C. Walsh;A. McMorland;G. Funk
1用新生小鼠(出生后0~3d)节律活跃的延髓切片标本，观察作用于NK1受体的P物质对舌下运动神经元兴奋性和吸气活动的影响。2局部应用NK1激动剂[SAR9，Met(O2)11]-SP(SPNK1)可使非特异性NK受体拮抗剂Spantide和NK1拮抗剂GR82334敏感地增加XII神经的吸气爆发幅度。3在电流钳下，SPNK1显著去极化XII-MN，增强对注入电流的重复放电反应，并使放电频率-电流关系左移，而不影响斜率。4电压钳下，SPNK1诱发内向电流，增加输入电阻，但对吸气性突触电流无影响。SPNK1电流在TTX存在时持续存在，是GR82334敏感的，随着超极化而减弱，并在预期的EK附近逆转。5去甲肾上腺素受体激动剂苯肾上腺素(PE)对重复放电行为的影响与α1基本相同。此外，SPNK1电流被PE完全阻断，提示共同的细胞内通路介导了NK1和α1去甲肾上腺素能受体的作用。尽管SPNK1和PE对XII MN对躯体注射电流的反应具有相似的作用，但α1去甲肾上腺素能受体的激活增强了吸气突触电流，并且在增强XII神经吸气爆发幅度方面的作用是后者的两倍多。6 GR82334使XII神经吸气爆发波幅降低，并在XII MNS产生小的外向电流。这些观察结果，以及首次在新生儿SPNK1敏感的吸气性XII MN附近发现SP免疫阳性终末的免疫组织化学证据，支持SP对XII MN兴奋性的内源性调节。7与膈MNS形成对比(Ptak et al.2 0 0 0年)，AP5阻断NMDA受体对SPNK1对XII神经活动的调节无影响。8综上所述，SPNK1主要通过抑制静息的突触后K+泄漏电导来调节XII运动神经元对吸气驱动的反应。这些结果证实了SP在出生后早期控制上呼吸道张力的功能意义，并提示SP对控制呼吸道和泵肌的运动神经元有不同的调节作用。
1 The effects of substance P (SP), acting at NK1 receptors, on the excitability and inspiratory activity of hypoglossal (XII) motoneurons (MNs) were investigated using rhythmically active medullary‐slice preparations from neonatal mice (postnatal day 0‐3). 2 Local application of the NK1 agonist [SAR9,Met (O2)11]‐SP (SPNK1) produced a dose‐dependent, spantide‐ (a non‐specific NK receptor antagonist) and GR82334‐(an NK1 antagonist) sensitive increase in inspiratory burst amplitude recorded from XII nerves. 3 Under current clamp, SPNK1 significantly depolarized XII MNs, potentiated repetitive firing responses to injected currents and produced a leftward shift in the firing frequency‐current relationships without affecting slope. 4 Under voltage clamp, SPNK1 evoked an inward current and increased input resistance, but had no effect on inspiratory synaptic currents. SPNK1 currents persisted in the presence of TTX, were GR82334 sensitive, were reduced with hyperpolarization and reversed near the expected EK. 5 Effects of the α1‐noradrenergic receptor agonist phenylephrine (PE) on repetitive firing behaviour were virtually identical to those of SPNK1. Moreover, SPNK1 currents were completely occluded by PE, suggesting that common intracellular pathways mediate the actions of NK1 and α1‐noradrenergic receptors. In spite of the similar actions of SPNK1 and PE on XII MN responses to somally injected current, α1‐noradrenergic receptor activation potentiated inspiratory synaptic currents and was more than twice as effective in potentiating XII nerve inspiratory burst amplitude. 6 GR82334 reduced XII nerve inspiratory burst amplitude and generated a small outward current in XII MNs. These observations, together with the first immunohistochemical evidence in the newborn for SP immunopositive terminals in the vicinity of SPNK1‐sensitive inspiratory XII MNs, support the endogenous modulation of XII MN excitability by SP. 7 In contrast to phrenic MNs ( Ptak et al. 2000 ), blocking NMDA receptors with AP5 had no effect on the modulation of XII nerve activity by SPNK1. 8 In conclusion, SPNK1 modulates XII motoneuron responses to inspiratory drive primarily through inhibition of a resting, postsynaptic K+ leak conductance. The results establish the functional significance of SP in controlling upper airway tone during early postnatal life and indicate differential modulation of motoneurons controlling airway and pump muscles by SP.
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DOI：
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发表时间：
1990
期刊：
Progress in clinical and biological research
影响因子：
--
作者：
BartlettJr,D;Leiter,JC;Knuth,SL
通讯作者：
Knuth,SL
影响因子：
56.9
作者：
SMITH, JC;ELLENBERGER, HH;FELDMAN, JL
通讯作者：
FELDMAN, JL
麻醉猫的呼吸需要腹外侧延髓中的兴奋性氨基酸。
DOI：
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发表时间：
1991
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Abrahams,TP;Hornby,PJ;Walton,DP;TaveiraDaSilva,AM;Gillis,RA
通讯作者：
Gillis,RA
影响因子：
5.5
作者：
GREER, JJ;SMITH, JC;FELDMAN, JL
通讯作者：
FELDMAN, JL
影响因子：
3.3
作者：
HUDGEL, DW;HARASICK, T
通讯作者：
HARASICK, T