Developmental nicotine exposure alters neurotransmission and excitability in hypoglossal motoneurons.
Developmental nicotine exposure alters neurotransmission and excitability in hypoglossal motoneurons.
复制标题
发育期尼古丁暴露会改变舌下运动神经元的神经传递和兴奋性。
DOI：
10.1152/jn.00876.2010
复制
发表时间：
2011
影响因子：
2.5
通讯作者：
Fregosi,RalphF
中科院分区：
文献类型：
--
作者：
Pilarski,JasonQ;Wakefield,HilaryE;Fuglevand,AndrewJ;Levine,RichardB;Fregosi,RalphF
舌下神经运动神经元（XII MNs）控制哺乳动物舌头的肌肉，并在呼吸期间有节奏地活跃。乙酰胆碱（ACh）通过促进表达烟碱ACh受体（nAChR）的神经元释放谷氨酸来调节XII MN活性。慢性尼古丁暴露会改变整个大脑神经元上的nAChR，包括脑干呼吸神经元。在这里，我们测试的假设，发育尼古丁暴露（DNE）减少兴奋性突触输入到XII MN。在有节律活动的延髓脑片中的电压钳实验显示，DNE动物的XII MN上的兴奋性突触后电流（EPSC）的频率降低了61%（DNE = 1.7 ± 0.4事件/s;对照= 4.4 ± 0.6事件/s;P< 0.002）。我们还检查了XII MNs的内在兴奋性，以测试来自DNE动物的细胞是否改变了膜特性。电流钳实验表明，来自DNE动物的XII MN具有更高的内在兴奋性，通过测量它们对注入电流的反应来评估。DNE细胞具有高输入电阻（DNE = 131.9 ± 13.7 MΩ，对照组= 78.6 ± 9.7 MΩ，P< 0.008），在较低电流水平下开始放电（DNE = 144 ± 22 pA，对照= 351 ± 45 pA，P< 0.003），并表现出较高的频率-电流增益值（DNE = 0.087 ± 0.012Hz/pA，对照= 0.050 ± 0.004Hz/pA，P< 0.02）。综上所述，我们的数据显示了以前未报道的DNE对XII MN功能的影响，也可能有助于解释DNE与中枢性和阻塞性呼吸暂停发病率之间的关系。
Hypoglossal motoneurons (XII MNs) control muscles of the mammalian tongue and are rhythmically active during breathing. Acetylcholine (ACh) modulates XII MN activity by promoting the release of glutamate from neurons that express nicotinic ACh receptors (nAChRs). Chronic nicotine exposure alters nAChRs on neurons throughout the brain, including brain stem respiratory neurons. Here we test the hypothesis that developmental nicotine exposure (DNE) reduces excitatory synaptic input to XII MNs. Voltage-clamp experiments in rhythmically active medullary slices showed that the frequency of excitatory postsynaptic currents (EPSCs) onto XII MNs from DNE animals is reduced by 61% (DNE = 1.7 ± 0.4 events/s; control = 4.4 ± 0.6 events/s;P< 0.002). We also examine the intrinsic excitability of XII MNs to test whether cells from DNE animals have altered membrane properties. Current-clamp experiments showed XII MNs from DNE animals had higher intrinsic excitability, as evaluated by measuring their response to injected current. DNE cells had high-input resistances (DNE = 131.9 ± 13.7 MΩ, control = 78.6 ± 9.7 MΩ,P< 0.008), began firing at lower current levels (DNE = 144 ± 22 pA, control = 351 ± 45 pA,P< 0.003), and exhibited higher frequency–current gain values (DNE = 0.087 ± 0.012 Hz/pA, control = 0.050 ± 0.004 Hz/pA,P< 0.02). Taken together, our data show previously unreported effects of DNE on XII MN function and may also help to explain the association between DNE and the incidence of central and obstructive apneas.