Opioid receptor activation modulates the calcium current in the cochlear outer hair cells of the rat

Abstract

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 2+ 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 2+ currents in a partially reversible form. Coincidently, norbinaltorphimine (a κ receptor antagonist) blocked the U-50488 inhibitory effect on the Ca 2+ current. The δ and the μ opioid receptor agonists did not significantly affect the Ca 2+ currents. These results indicate that the κ opioid receptor activation inhibits the Ca 2+ current in OHC, modulating the intracellular Ca 2+ 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.

Experience-dependent flexibility in a molecularly diverse central-to-peripheral auditory feedback system

“…LOCs have been reported to express a wide range of transmitters, peptides, and modulators in the past, but definitive evidence for many has been lacking. Our data rule out a major role for LOC transmission of opioid peptides 36,89 , which were detected by neither RNA-seq nor FISH (Figure S4G, H). On the other hand, our data identify a new transmitter in the LOC repertoire, NPY.…”