Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico.
Eur J Neurosci. 2022 Jul;56(1):3543-3552. doi: 10.1111/ejn.15682. Epub 2022 May 10.
Previous works showed that opioid peptides are produced by olivocochlear efferent neurons, while cochlear hair cells express opioid receptors. It has been proposed that opioids protect the auditory system from damage by intense stimulation, although their use for therapeutic or illicit purposes links to hearing impairment. Therefore, it is relevant to study the effect of opioids in the auditory system to define their functional expression and mechanism of action. This study investigated the modulation of the Ca currents by opioid peptides in the rat outer hair cells (OHC) using the whole-cell patch-clamp technique. The influence of agonists of the three opioid receptor subtypes (μ, δ, and κ) was studied. The κ opioid receptor agonist U-50488 inhibits the Ca currents in a partially reversible form. Coincidently, norbinaltorphimine (a κ receptor antagonist) blocked the U-50488 inhibitory effect on the Ca current. The δ and the μ opioid receptor agonists did not significantly affect the Ca currents. These results indicate that the κ opioid receptor activation inhibits the Ca current in OHC, modulating the intracellular Ca concentration when OHCs depolarize. The modulation of the auditory function by opioids constitutes a relevant mechanism with a potential role in the physiopathology of auditory disturbances.
先前的研究表明，阿片肽由橄榄耳蜗传出神经元产生，而耳蜗毛细胞表达阿片受体。有人提出，阿片类物质通过保护听觉系统免受强烈刺激的损伤，尽管它们被用于治疗或非法目的与听力损伤有关。因此，研究阿片类物质在听觉系统中的作用对于确定其功能表达和作用机制是很重要的。本研究采用全细胞膜片钳技术研究了阿片肽对大鼠外毛细胞（OHC）Ca 电流的调制作用。研究了三种阿片受体亚型（μ、δ和κ）激动剂的影响。κ阿片受体激动剂 U-50488 以部分可逆的形式抑制 Ca 电流。同时，norbinaltorphimine（一种 κ 受体拮抗剂）阻断了 U-50488 对 Ca 电流的抑制作用。δ和μ阿片受体激动剂对 Ca 电流没有显著影响。这些结果表明，κ 阿片受体的激活抑制了 OHC 中的 Ca 电流，当 OHC 去极化时，调节细胞内 Ca 浓度。阿片类物质对听觉功能的调制构成了一个相关的机制，在听觉障碍的病理生理学中可能具有潜在作用。
