Ampakine CX717 potentiates intermittent hypoxia-induced hypoglossal long-term facilitation.
Ampakine CX717 potentiates intermittent hypoxia-induced hypoglossal long-term facilitation.
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Ampakine CX717 增强间歇性缺氧引起的舌下长期促进作用。
DOI：
10.1152/jn.00210.2016
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发表时间：
2016
影响因子：
2.5
通讯作者：
Fuller,DD
中科院分区：
文献类型：
--
作者：
Turner,SM;ElMallah,MK;Hoyt,AK;Greer,JJ;Fuller,DD
谷氨酸能电流在调节呼吸运动输出中起重要作用，并且在整个运动前和运动呼吸回路中部分由α-氨基-3-羟基-5-甲基-异恶唑-丙酸（AMPA）受体介导。Ampakines是通过改变AMPA受体通道动力学来增强多巴胺能传递的药理学化合物。在这里，我们研究了ampakines是否改变呼吸长时程易化（LTF）的表达，LTF是一种神经可塑性形式，表现为短暂的低氧[间歇性缺氧（IH）]后吸气活动的持续增加。目前的突触模型表明，增强的有效性，肾上腺素能突触后IH，我们假设，ampakine预处理将加强IH诱导的LTF的呼吸活动。从麻醉和机械通气的小鼠的舌下神经记录吸气爆发。在基线（BL）记录条件下，爆发振幅稳定至少90 min（98 ± 5% BL）。暴露于IH（3 × 1 min，15% O2）导致爆发振幅持续增加（最后一次缺氧后90 min时为218 ± 44% BL）。在IH前10 min腹腔注射ampakine CX 717（15 mg/kg）的小鼠显示LTF增强（90 min时为500 ± 110% BL）。事后分析表明，CX 717仅在初始基线爆发振幅较低时增强LTF。我们的结论是，在适当的条件下，ampakine预处理可以增强IH诱导的呼吸LTF。这些数据表明，ampakines可能有治疗价值的背景下，缺氧为基础的神经康复策略，特别是在呼吸运动输出功能障碍，如脊髓损伤。
Glutamatergic currents play a fundamental role in regulating respiratory motor output and are partially mediated by α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors throughout the premotor and motor respiratory circuitry. Ampakines are pharmacological compounds that enhance glutamatergic transmission by altering AMPA receptor channel kinetics. Here, we examined if ampakines alter the expression of respiratory long-term facilitation (LTF), a form of neuroplasticity manifested as a persistent increase in inspiratory activity following brief periods of reduced O2[intermittent hypoxia (IH)]. Current synaptic models indicate enhanced effectiveness of glutamatergic synapses after IH, and we hypothesized that ampakine pretreatment would potentiate IH-induced LTF of respiratory activity. Inspiratory bursting was recorded from the hypoglossal nerve of anesthetized and mechanically ventilated mice. During baseline (BL) recording conditions, burst amplitude was stable for at least 90 min (98 ± 5% BL). Exposure to IH (3 × 1 min, 15% O2) resulted in a sustained increase in burst amplitude (218 ± 44% BL at 90 min following final bout of hypoxia). Mice given an intraperitoneal injection of ampakine CX717 (15 mg/kg) 10 min before IH showed enhanced LTF (500 ± 110% BL at 90 min). Post hoc analyses indicated that CX717 potentiated LTF only when initial baseline burst amplitude was low. We conclude that under appropriate conditions ampakine pretreatment can potentiate IH-induced respiratory LTF. These data suggest that ampakines may have therapeutic value in the context of hypoxia-based neurorehabilitation strategies, particularly in disorders with blunted respiratory motor output such as spinal cord injury.