The University of Arizona, College of Medicine, Department of Physiology, P.O. Box 210093, Tucson, AZ 85721-0093, USA.
J Neurophysiol. 2011 Jan;105(1):423-33. doi: 10.1152/jn.00876.2010. Epub 2010 Nov 10.
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.
舌下运动神经元（XII MNs）控制哺乳动物舌头的肌肉，在呼吸过程中呈节律性活动。乙酰胆碱（ACh）通过促进表达烟碱型乙酰胆碱受体（nAChRs）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中的神经元的 nAChRs，包括脑干呼吸神经元。在这里，我们检验了这样一个假设，即发育性尼古丁暴露（DNE）会减少对 XII MN 的兴奋性突触输入。在节律性活跃的延髓切片中进行电压钳实验表明，来自 DNE 动物的 XII MN 的兴奋性突触后电流（EPSC）频率降低了 61%（DNE = 1.7 ± 0.4 个事件/s；对照 = 4.4 ± 0.6 个事件/s；P < 0.002）。我们还检查了 XII MN 的内在兴奋性，以测试来自 DNE 动物的细胞是否具有改变的膜特性。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，这可以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 = 78.6 ± 9.7 MΩ，P < 0.008），在较低的电流水平下开始放电（DNE = 144 ± 22 pA，对照 = 351 ± 45 pA，P < 0.003），并且表现出更高的频率-电流增益值（DNE = 0.087 ± 0.012 Hz/pA，对照 = 0.050 ± 0.004 Hz/pA，P < 0.02）。总之，我们的数据显示了以前未报道的 DNE 对 XII MN 功能的影响，这也可能有助于解释 DNE 与中枢性和阻塞性呼吸暂停发生率之间的关联。
