Dopaminergic Inhibition of Na+ Currents in Vestibular Inner Ear Afferents

Frances L Meredith,Katherine J Rennie

doi:10.3389/fnins.2021.710321

Frances L Meredith, Katherine J Rennie

Open Access

https://doi.org/10.3389/fnins.2021.710321

Copy DOI

Abstract

Inner ear hair cells form synapses with afferent terminals and afferent neurons carry signals as action potentials to the central nervous system. Efferent neurons have their origins in the brainstem and some make synaptic contact with afferent dendrites beneath hair cells. Several neurotransmitters have been identified that may be released from efferent terminals to modulate afferent activity. Dopamine is a candidate efferent neurotransmitter in both the vestibular and auditory systems. Within the cochlea, activation of dopamine receptors may reduce excitotoxicity at the inner hair cell synapse via a direct effect of dopamine on afferent terminals. Here we investigated the effect of dopamine on sodium currents in acutely dissociated vestibular afferent calyces to determine if dopaminergic signaling could also modulate vestibular responses. Calyx terminals were isolated along with their accompanying type I hair cells from the cristae of gerbils (P15-33) and whole cell patch clamp recordings performed. Large transient sodium currents were present in all isolated calyces; compared to data from crista slices, resurgent Na+ currents were rare. Perfusion of dopamine (100 μM) in the extracellular solution significantly reduced peak transient Na+ currents by approximately 20% of control. A decrease in Na+ current amplitude was also seen with extracellular application of the D2 dopamine receptor agonist quinpirole, whereas the D2 receptor antagonist eticlopride largely abolished the response to dopamine. Inclusion of the phosphatase inhibitor okadaic acid in the patch electrode solution occluded the response to dopamine. The reduction in calyx sodium current in response to dopamine suggests efferent signaling through D2 dopaminergic receptors may occur via common mechanisms to decrease excitability in inner ear afferents.

Highlights

The inner ear houses the cochlea and vestibular system where signals relevant to auditory and vestibular perception are processed by hair cells and carried to the brain by their companion afferent nerve fibers
Efferent fibers emanate from the brainstem to make synapses with type II hair cells and with afferent dendrites including the outer aspects of large calyx terminals surrounding type I hair cells (Wersall, 1956)
Efferent release of acetylcholine can produce excitation through the muscarinic inhibition of K+ currents mediated by KCNQ channels in calyx-bearing afferents (Holt et al, 2017; Lee et al, 2017)

Summary

Introduction

The inner ear houses the cochlea and vestibular system where signals relevant to auditory and vestibular perception are processed by hair cells and carried to the brain by their companion afferent nerve fibers. In mammals outer and inner hair cells are found in the cochlea, whereas type I and type II hair cells populate the sensory epithelia of the vestibular organs. Medial olivocochlear efferents terminate on outer hair cells and lateral olivocochlear neurons make synapses with afferent nerve fibers beneath inner hair cells (Warr and GuinanJr., 1979). Efferent fibers emanate from the brainstem to make synapses with type II hair cells and with afferent dendrites including the outer aspects of large calyx terminals surrounding type I hair cells (Wersall, 1956). Efferent release of acetylcholine can produce excitation through the muscarinic inhibition of K+ currents mediated by KCNQ channels in calyx-bearing afferents (Holt et al, 2017; Lee et al, 2017)

Methods

Results

Discussion

Conclusion