Neurokinin-1 receptors modulate the excitability of expiratory neurons in the ventral respiratory group.
Neurokinin-1 receptors modulate the excitability of expiratory neurons in the ventral respiratory group.
复制标题
Neurokinin-1 受体调节腹侧呼吸组呼气神经元的兴奋性。
DOI：
10.1152/jn.00864.2007
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发表时间：
2008
影响因子：
2.5
通讯作者：
Potts,JeffreyT
中科院分区：
文献类型：
--
作者：
Fong,AngelinaY;Potts,JeffreyT
我们研究了神经激肽-1受体（NK1-R）对包括Bötzinger复合体（BötC）在内的整个腹侧呼吸组呼气(E)神经元（强直性放电，ETONIC；增强，EAUG；减少，EDEC）兴奋性的作用，使用细胞外单单位记录结合加压皮射，动脉灌注的大鼠。在选择性NK1-R拮抗剂CP99,994之前和之后，测定了NK1-R激动剂[Sar9-Met(O2)11]- P物质（SSP）的皮射引起的反应。SSP刺激了35个呼气神经元中的20个，增加了每次爆发的动作电位数（对照组的+33.7±6.5%）、爆发持续时间（对照组的+20.6±7.9%）和峰值放电频率（对照组的+16.2±4.8%，平均值±SE）。CP99,994预处理完全阻断了部分被测神经元的SSP诱发兴奋，支持了通过NK1-R激活介导SSP兴奋的观点。由于我们之前已经证明eaugneuron对运动-呼吸耦合（LRC）至关重要，我们推断NK1-R的阻断会通过阻止eaugneuron的躯体诱发兴奋来改变LRC。CP99,994阻断BötC中NK1-Rs严重破坏LRC，阻止eaugneuron的体诱发兴奋。这些发现表明LRC依赖于内源性SP释放，通过NK1-Rs作用于BötC的eaugneuron。结合我们之前的研究发现，Hering-Breuer反射的吸气关闭需要内源性NK1-Rs的激活，通过激活edecneuron上的NK1-Rs，我们认为BötC中P物质的内源性释放提供了一种反射通路依赖的机制来选择性地调节呼吸节律。
We studied the role of neurokinin-1 receptors (NK1-R) on the excitability of expiratory (E) neurons (tonic discharge, ETONIC; augmenting, EAUG; decrementing, EDEC) throughout the ventral respiratory group, including Bötzinger Complex (BötC) using extracellular single-unit recording combined with pressurized picoejection in decerebrate, arterially perfused juvenile rats. Responses evoked by picoejection of the NK1-R agonist, [Sar9-Met(O2)11]-substance P (SSP) were determined before and after the selective NK1-R antagonist, CP99,994. SSP excited 20 of 35 expiratory neurons by increasing the number of action potentials per burst (+33.7 ± 6.5% of control), burst duration (+20.6 ± 7.9% of control), and peak firing frequency (+16.2 ± 4.8% of control; means ± SE). Pretreatment with CP99,994 completely blocked SSP-evoked excitation in a subset of neurons tested, supporting the notion that SSP excitation was mediated through NK1-R activation. Because we had previously shown that EAUGneurons were crucial to locomotor-respiratory coupling (LRC), we reasoned that blockade of NK1-R would alter LRC by preventing somatic-evoked excitation of EAUGneurons. Blockade of NK1-Rs by CP99,994 in the BötC severely disrupted LRC and prevented somatic-evoked excitation of EAUGneurons. These findings demonstrate that LRC is dependent on endogenous SP release acting via NK1-Rs on EAUGneurons of the BötC. Taken together with our earlier finding that inspiratory off-switching by the Hering-Breuer Reflex requires endogenous activation of NK1-Rs through activation of NK1-Rs on EDECneurons, we suggest that endogenous release of substance P in the BötC provides a reflex pathway-dependent mechanism to selectively modulate respiratory rhythm.