Inflammation can increase the excitability of bronchopulmonary C-fibers leading to excessive sensations and reflexes (e.g. wheeze and cough). We have previously shown modulation of peripheral nerve terminal mitochondria by antimycin A causes hyperexcitability in TRPV1-expressing bronchopulmonary C-fibers through the activation of protein kinase C (PKC). Here, we have investigated the PKC isoform responsible for this signaling. We found PKCβ1, PKCδ and PKCε were expressed by many vagal neurons, with PKCα and PKCβ2 expressed by subsets of vagal neurons. In dissociated vagal neurons, antimycin A caused translocation of PKCα but not the other isoforms, and only in TRPV1-lineage neurons. In bronchopulmonary C-fiber recordings, antimycin A increased the number of action potentials evoked by α,β-methylene ATP. Selective inhibition of PKCα, PKCβ1 and PKCβ2 with 50 nM bisindolylmaleimide I prevented the antimycin-induced bronchopulmonary C-fiber hyperexcitability, whereas selective inhibition of only PKCβ1 and PKCβ2 with 50 nM LY333531 had no effect. We therefore conclude that PKCα is required for antimycin-induced increases in bronchopulmonary C-fiber excitability.

中文翻译：

---

抗霉素 A 通过蛋白激酶 C α 增加支气管肺 C 纤维的兴奋性。

炎症会增加支气管肺 C 纤维的兴奋性，导致过度的感觉和反射（例如喘息和咳嗽）。我们之前已经表明，抗霉素 A 对周围神经末梢线粒体的调节会通过激活蛋白激酶 C (PKC) 导致表达 TRPV1 的支气管肺 C 纤维的过度兴奋。在这里，我们研究了负责这种信号的 PKC 同种型。我们发现 PKCβ1、PKCδ 和 PKCε 由许多迷走神经元表达，PKCα 和 PKCβ2 由迷走神经元亚群表达。在解离的迷走神经神经元中，抗霉素 A 引起 PKCα 易位，但不引起其他同种型的易位，并且仅在 TRPV1 谱系神经元中。在支气管肺 C 纤维记录中，抗霉素 A 增加了由 α,β-亚甲基 ATP 诱发的动作电位的数量。PKCα 的选择性抑制，PKCβ1 和 PKCβ2 与 50 nM 双吲哚基马来酰亚胺 I 阻止了抗霉素诱导的支气管肺 C 纤维过度兴奋，而仅 PKCβ1 和 PKCβ2 与 50 nM LY333531 的选择性抑制没有效果。因此，我们得出结论，抗霉素诱导的支气管肺 C 纤维兴奋性增加需要 PKCα。