Revill Ann L, Katzell Alexis, Del Negro Christopher A, Milsom William K, Funk Gregory D
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada.
Department of Physiology, University of Alberta, Edmonton, AB, Canada.
Front Physiol. 2021 Apr 13;12:626470. doi: 10.3389/fphys.2021.626470. eCollection 2021.
The pre-Bötzinger complex (preBötC) of the ventral medulla generates the mammalian inspiratory breathing rhythm. When isolated in explants and deprived of synaptic inhibition, the preBötC continues to generate inspiratory-related rhythm. Mechanisms underlying burst generation have been investigated for decades, but cellular and synaptic mechanisms responsible for burst termination have received less attention. KCNQ-mediated K currents contribute to burst termination in other systems, and their transcripts are expressed in preBötC neurons. Therefore, we tested the hypothesis that KCNQ channels also contribute to burst termination in the preBötC. We recorded KCNQ-like currents in preBötC inspiratory neurons in neonatal rat slices that retain respiratory rhythmicity. Blocking KCNQ channels with XE991 or linopirdine (applied superfusion or locally) increased inspiratory burst duration by 2- to 3-fold. By contrast, activation of KCNQ with retigabine decreased inspiratory burst duration by ~35%. These data from reduced preparations suggest that the KCNQ current in preBötC neurons contributes to inspiratory burst termination.
延髓腹侧的前包钦格复合体（preBötC）产生哺乳动物的吸气呼吸节律。当在脑片培养物中分离并去除突触抑制时，preBötC仍能继续产生与吸气相关的节律。数十年来，人们一直在研究爆发式发放产生的机制，但负责爆发式发放终止的细胞和突触机制却较少受到关注。KCNQ介导的钾电流在其他系统中有助于爆发式发放的终止，并且它们的转录本在preBötC神经元中表达。因此，我们检验了KCNQ通道也有助于preBötC爆发式发放终止的假说。我们在保留呼吸节律性的新生大鼠脑片的preBötC吸气神经元中记录到了类似KCNQ的电流。用XE991或利诺吡啶（通过灌流或局部应用）阻断KCNQ通道，可使吸气爆发持续时间增加2至3倍。相比之下，用瑞替加滨激活KCNQ可使吸气爆发持续时间减少约35%。这些来自简化标本的数据表明，preBötC神经元中的KCNQ电流有助于吸气爆发的终止。
