Characterizing the Role of Kcnq5a in Zebrafish Inner Ear Hair Cells

Abstract

Hair cells (HCs) are specialized mechanoreceptors in the vertebrate inner ear that function in hearing and balance. Non‐mammalian HCs have electrophysiological properties that resemble both that of mammalian vestibular or cochlear HCs, including mechanotransduction, as well as potassium ion (K+) and calcium ion (Ca2+) currents. While mammals rely upon mechanical mechanisms to generate tuned receptor potentials, non‐mammalian HCs exhibit electrical resonance, a unique feature for frequency tuning of HCs that is modulated by voltage‐dependent conductances. In non‐mammalian HCs, the channel kinetics and interplay of K+ and Ca2+ channels result in oscillation of the membrane potential, generating electrical resonance that enhances the frequency tuning of the HCs. However, the molecular identity of the channels involved in electrical resonance in non‐mammalian HCs remains largely unknown. This study focused on kcnq5a, a gene encoding the voltage‐dependent potassium channel KQT‐like subfamily member 5a (Kcnq5a). The channels of the KCNQ gene family are responsible for generating sub‐threshold M‐currents in neurons, stabilizing resting membrane potential and thereby influencing cell excitability. We hypothesized that Kcnq5a is responsible for generating electrical resonance and maintaining resting membrane potential of zebrafish inner ear HCs. Both RT‐qPCR and in situ hybridization studies confirmed that kcnq5a was expressed in HCs of the inner ear. To characterize the function of the Kcnq5a channel in inner ear HCs, morpholinos were injected into one‐cell stage embryos for targeted knockdown of kcnq5a mRNA. Morphology of HCs in both injected and wildtype zebrafish was examined with confocal microscopy. Auditory function was measured using microphonic responses of otolithic organs in larval zebrafish, while auditory sensitivity was measured using a behavioral prepulse inhibition assay. Following knockdown of kcnq5a, the larvae (5dpf) showed a decrease in microphonic amplitude and hearing threshold. This study represents a preliminary examination of the role of Kcnq5a in electrical resonance and frequency selectivity in zebrafish inner ear HCs.Support or Funding InformationThis work has been supported by the NIH grant R01 DC 016807‐01 to Dr. David HeThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.