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首页> 外文期刊>Journal of Neurophysiology >Adrenergic agonist induces rhythmic firing in quiescent cardiac preganglionic neurons in nucleus ambiguous via activation of intrinsic membrane excitability
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Adrenergic agonist induces rhythmic firing in quiescent cardiac preganglionic neurons in nucleus ambiguous via activation of intrinsic membrane excitability

机译：肾上腺素能激动剂通过活化的内在膜兴奋性诱导核心心脏PREGANGLIONIC神经元的节奏烧制

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Cholinergic vagal nerves projecting from neurons in the brain stem nucleus ambiguus (NAm) play a predominant role in cardiac parasympathetic pacemaking control. Central adrenergic signaling modulates the tone of this vagal output; however, the exact excitability mechanisms are not fully understood. We investigated responses of NAm neurons to adrenergic agonists using in vitro mouse brain stem slices. Preganglionic NAm neurons were identified by ChAT-tdTomato fluorescence in young adult transgenic mice, and their cardiac projection was confirmed by retrograde dye tracing. Juxtacellular recordings detected sparse or absent spontaneous action potentials (AP) in NAm neurons. However, bath application of epinephrine or norepinephrine strongly and reversibly activated most NAm neurons regardless of their basal firing rate. Epinephrine was more potent than norepinephrine, and this activation largely depends on alpha(1)-adrenoceptors. Interestingly, adrenergic activation of NAm neurons does not require an ionotropic synaptic mechanism, because postsynaptic excitatory or inhibitory receptor blockade did not occlude the excitatory effect, and bath-applied adrenergic agonists did not alter excitatory or inhibitory synaptic transmission. Instead, adrenergic agonists significantly elevated intrinsic membrane excitability to facilitate generation of recurrent action potentials. T-type calcium current and hyperpolarization-activated current are involved in this excitation pattern, although not required for spontaneous AP induction by epinephrine. In contrast, pharmacological blockade of persistent sodium current significantly inhibited the adrenergic effects. Our results demonstrate that central adrenergic signaling enhances the intrinsic excitability of NAm neurons and that persistent sodium current is required for this effect. This central balancing mechanism may counteract excessive peripheral cardiac excitation during increased sympathetic tone.
机译：从脑干细胞核中的神经元突出的胆碱能迷离神经在心脏副交感神经起期症控制中起主要作用。中央肾上腺素能信号调制这种迷走输出的基调;然而，确切的激发性机制不完全理解。我们使用体外小鼠脑干切片研究了Nam神经元对肾上腺素能激动剂的反应。通过在年轻成年转基因小鼠中通过聊天-TDTOMATO荧光鉴定PREGANGLIONIC NAM神经元，并通过逆行染料跟踪证实了它们的心脏投影。 NAM神经元中检测到稀疏或缺乏自发动作电位（AP）的Juxtacellular记录。然而，无论其基础烧制率如何，肾上腺素或去甲肾上腺素的沐浴施用强烈且可逆地激活了大多数NAM神经元。肾上腺素比去甲肾上腺素更有效，这种活化在很大程度上取决于α（1） - 一种肾上腺素受体。有趣的是，Nam神经元的肾上腺素能活化不需要离子型突触机制，因为后腹泻兴奋剂或抑制性受体阻断并未闭塞兴奋性效果，并且浴应用的肾上腺素能激动剂没有改变兴奋性或抑制突触传递。相反，肾上腺素能激动剂显着提高了内在膜兴奋性，以促进产生复发动作电位。 T型钙电流和超极化激活电流涉及该激发图案，但不需要通过肾上腺素诱导自发AP诱导。相比之下，持久性钠电流的药理阻滞显着抑制了肾上腺素能作用。我们的结果表明，中枢肾上腺素能信号传导增强了NAM神经元的内在兴奋性，并且这种效果需要持续钠电流。这种中央平衡机构可以在增加的交感神经音调期间抵消过度外围心脏激发。

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