Inspiratory rhythm generation is stabilized by Ih.
Inspiratory rhythm generation is stabilized by Ih.
复制标题
吸气节律的产生由 Ih 稳定。
DOI：
10.1152/jn.00150.2022
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发表时间：
2022
影响因子：
2.5
通讯作者：
Ramirez,Jan-Marino
中科院分区：
文献类型：
--
作者：
Burgraff,NicholasJ;Phillips,RyanS;Severs,LizaJ;Bush,NicholasE;Baertsch,NathanA;Ramirez,Jan-Marino
细胞和网络特性必须能够产生灵活而稳定的节律活动。这对呼吸尤其重要，呼吸是一种有节奏的行为，从第一次呼吸到最后一次呼吸，它动态地适应环境，行为和代谢变化。位于延髓腹侧的前波青格复合体（pre-BötC）负责产生节律性吸气。它的细胞特性必须是可调的，灵活的以及稳定的。在这里，我们探讨了超极化激活，非选择性阳离子电流（Ih）的作用，在阿片类药物暴露和减少兴奋性突触传递过程中稳定前BötC活性。将Ih引入计算机预BötC网络预测，该去极化电流的损失应显著减慢吸气节律。相比之下，体外和体内实验表明，Ih的损失对呼吸频率的影响最小，但通过产生不完全同步的爆发（burstlets）使节律发生不稳定。与Ih丢失相关的是呼吸对阿片类药物诱导的呼吸抑制或兴奋性突触相互作用减弱的易感性增加，细胞水平上的反常去极化和强直性尖峰抑制。紧张性尖峰活动由非节律性兴奋性和抑制性前BötC神经元产生，其中大部分表达Ih。总之，我们的研究结果表明，Ih电流对维持紧张性尖峰、稳定吸气节律和保护呼吸免受网络状态的扰动或变化很重要。该电流对于促进兴奋性和抑制性神经元中的内在紧张性尖峰活动以及在抑制网络兴奋性的条件下（例如在阿片类药物诱导的呼吸抑制的情况下）保持节律功能是重要的。因此，我们认为Ih电流扩大了节律发生的动态范围，缓冲了preBötC对网络扰动的影响，并通过防止非同步爆发的产生来稳定节律发生。https://jneurophysiol.podbean.com/e/four-questions-from-the-journal-of-neurophysiology-jan-marino-ramirez-and-nicholas-j-burgraff/
Cellular and network properties must be capable of generating rhythmic activity that is both flexible and stable. This is particularly important for breathing, a rhythmic behavior that dynamically adapts to environmental, behavioral, and metabolic changes from the first to the last breath. The pre-Bötzinger complex (preBötC), located within the ventral medulla, is responsible for producing rhythmic inspiration. Its cellular properties must be tunable, flexible as well as stabilizing. Here, we explore the role of the hyperpolarization-activated, nonselective cation current (Ih) for stabilizing PreBötC activity during opioid exposure and reduced excitatory synaptic transmission. IntroducingIhinto an in silico preBötC network predicts that loss of this depolarizing current should significantly slow the inspiratory rhythm. By contrast, in vitro and in vivo experiments revealed that the loss ofIhminimally affected breathing frequency, but destabilized rhythmogenesis through the generation of incompletely synchronized bursts (burstlets). Associated with the loss ofIhwas an increased susceptibility of breathing to opioid-induced respiratory depression or weakened excitatory synaptic interactions, a paradoxical depolarization at the cellular level, and the suppression of tonic spiking. Tonic spiking activity is generated by nonrhythmic excitatory and inhibitory preBötC neurons, of which a large percentage expressIh. Together, our results suggest thatIhis important for maintaining tonic spiking, stabilizing inspiratory rhythmogenesis, and protecting breathing against perturbations or changes in network state.NEW & NOTEWORTHYTheIhcurrent plays multiple roles within the preBötC. This current is important for promoting intrinsic tonic spiking activity in excitatory and inhibitory neurons and for preserving rhythmic function during conditions that dampen network excitability, such as in the context of opioid-induced respiratory depression. We therefore propose that theIhcurrent expands the dynamic range of rhythmogenesis, buffers the preBötC against network perturbations, and stabilizes rhythmogenesis by preventing the generation of unsynchronized bursts.Listen to this article’s corresponding podcast at https://jneurophysiol.podbean.com/e/four-questions-from-the-journal-of-neurophysiology-jan-marino-ramirez-and-nicholas-j-burgraff/.