气味诱发钾电流对哺乳动物嗅觉反应的调节作用

IF 3.3 Q2 ALLERGY
Frontiers in allergy Pub Date : 2024-10-16 eCollection Date: 2024-01-01 DOI:10.3389/falgy.2024.1478529
Samantha Hagerty, Oleg Pustovyy, Ludmila Globa, Vitaly Vodyanoy, Melissa Singletary
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引用次数: 0

摘要

众所周知,气味会与嗅觉神经元(OSN)纤毛膜上的特异性 G 蛋白偶联受体相互作用,从而启动一连串由电压产生的细胞内信号转导事件,这些事件可在上皮水平记录为电泳图(EOG)。脊椎动物的去极化兴奋通路涉及环磷酸腺苷(cAMP)诱导的 Na+/Ca2+ 流入和钙诱导的 Cl- 流出,这一通路已得到公认,但也有证据表明,钾相关抑制电流与细胞活化相对应。虽然几种依赖 Ca2+ 的反馈机制有助于细胞失活,通常被认为是这些抑制性电流的作用,但在兴奋性去极化之前经常观察到的正离子传导,使许多人认为在受体水平上存在另一种早期抑制机制,这种机制可能与下游钙离子流入无关。由于结论相互矛盾,人们对嗅觉细胞中独立于 Ca2+ 的抑制电流的作用和机制还不完全清楚。我们通过比较大鼠嗅觉上皮在离子通道抑制和有针对性地激活下游成分(无论是否有钾阻断)后的电泳图(EOG)记录,研究了钾通道在气味传导中的功能和时间参与。几种 K+ 通道阻断剂(4-氨基吡啶、charybdotoxin 和 iberiotoxin)显示了作用前电位正电流的减弱,这与对气味刺激的兴奋反应减弱相对应,而当去除阻断剂后,这种反应又会恢复。我们进一步评估了无气味或气味反应增强型纳米锌颗粒的 EOG 反应。在没有气味刺激的情况下,用磷酸二酯酶抑制剂 3-异丁基-1-甲基黄嘌呤(IBMX)结合 K+ 通道抑制剂化学激发膜兴奋,进一步表明钾通道激活先于兴奋事件,且独立于 cAMP 诱导的钙离子流入。这些结果支持了之前关于气味激活抑制性钾电流的发现,抑制性钾电流可能在随后的 G 蛋白活动中发挥功能性作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mediation of mammalian olfactory response by presence of odor-evoked potassium current.

It is well understood that odorants interact with specialized G-protein coupled receptors embedded in the ciliary membrane of olfactory sensory neurons (OSN) which initiates a voltage-generating intracellular cascade of signal transduction events that can be recorded at the epithelial level as an electroolfactogram (EOG). While the depolarizing excitatory pathway in vertebrates involving cyclic adenosine monophosphate (cAMP)-induced Na+/Ca2+ influx and calcium-induced Cl- efflux is well established, there is evidence of potassium-associated inhibitory currents that correspond with cellular activation. While several Ca2+-dependent feedback mechanisms contribute to cellular deactivation which have been commonly attributed to these inhibitory currents, the frequently observed positive ionic conductance prior to excitatory depolarization have led many to suggest an additional earlier inhibitory mechanism at the receptor level that may be independent of downstream calcium influx. Due to conflicting conclusions, the role and mechanism behind Ca2+-independent inhibitory currents in olfactory cells is not fully understood. We investigated the functional and temporal involvement of potassium channels in odor transduction by comparing electroolfactogram (EOG) recordings in rat olfactory epithelia following ion channel inhibition and targeted activation of downstream components with or without potassium-blocking. Several K+-channel blocking agents (4-Aminopyridine, charybdotoxin, & iberiotoxin) demonstrated a diminished pre-action potential positive current that corresponded with reduced excitatory response to odor stimulation that was recovered when blockers were removed. We further assessed EOG responses in the absence of odor or with odor response enhancing zinc nanoparticles. Chemically eliciting membrane excitation in the absence of odor stimulation with a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), in combination with K+-channel inhibition, further indicated potassium channel activation precedes excitatory events and is independent of cAMP-induced calcium influx. These results support previous findings of odor-activated inhibitory potassium currents that may play a functional role in subsequent G-protein activity.

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