Expression of a membrane-targeted fluorescent reporter disrupts auditory hair cell mechanoelectrical transduction and causes profound deafness.

AbstractThe stereocilia of the inner ear are unique cellular structures which correlate anatomically with distinct cochlear functions, including mechanoelectrical transduction, cochlear amplification, adaptation, frequency selectivity and tuning. Their function is impaired by inner ear stressors, by various types of hereditary deafness, syndromic hearing loss and inner ear disease (e.g. Ménière's disease). The anatomical and physiological characteristics of stereocilia are discussed in relation to inner ear malfunctions.

Download Full-text

Faculty Opinions recommendation of Auditory cortex interneuron development requires cadherins operating hair-cell mechanoelectrical transduction.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727807447.793535047 ◽

2017 ◽

Author(s):

Donna Fekete ◽

Vidhya Munnamalai

Keyword(s):

Auditory Cortex ◽

Hair Cell ◽

Mechanoelectrical Transduction ◽

Interneuron Development

Download Full-text

Endolymph Composition: Paradigm or Inevitability?

Physiological Research ◽

10.33549/physiolres.933684 ◽

2018 ◽

pp. 175-179 ◽

Cited By ~ 1

Author(s):

H. GAGOV ◽

M. CHICHOVA ◽

M. MLADENOV

Keyword(s):

Signal Transduction ◽

Cell Membrane ◽

Hair Cell ◽

Energy Saving ◽

Inner Ear ◽

Hair Cells ◽

Hypothetical Model ◽

Mechanoelectrical Transduction ◽

Normal Composition

This review is focused on the unusual composition of the endolymph of the inner ear and its function in mechanoelectrical transduction. The role of K+ and Ca2+ in excitatory influx, the very low Na+, Ca2+ and Mg2+ concentrations of endolymph, stereocilia structure of hair cells and some proteins involved in mechanosensory signal transduction with emphasis on auditory receptors are presented and analyzed in more details. An alternative hypothetical model of ciliary structure and endolymph with a ‘normal’ composition is discussed. It is concluded that the unique endolymph cation content is more than an energy saving mechanism that avoids disturbing circulatory vibrations to achieve a much better mechanosensory resolution. It is the only possible way to fulfil the requirements for a precise ciliary mechanoelectrical transduction in conditions where pressure events with quite diverse amplitudes and duration are transformed into adequate hair cell membrane depolarizations, which are regulated by a sensitive Ca2+-dependent feedback tuning.

Download Full-text

Expression of a membrane-targeted fluorescent reporter disrupts auditory hair cell mechanoelectrical transduction and causes profound deafness

10.1101/2020.09.18.303743 ◽

2020 ◽

Author(s):

Angela Ballesteros ◽

Tracy S. Fitzgerald ◽

Kenton J. Swartz

Keyword(s):

Hair Cells ◽

Otoacoustic Emissions ◽

Fluorescent Protein ◽

Super Resolution ◽

Auditory Brainstem ◽

Auditory Brainstem Responses ◽

Fluorescent Reporter ◽

Auditory Hair Cells ◽

Mechanoelectrical Transduction ◽

Distortion Product

AbstractThe reporter mT/mG mice expressing a membrane-targeted fluorescent protein are becoming widely used to study the auditory and vestibular system due to its versatility. Here we show that high expression levels of the fluorescent mtdTomato reporter affect the function of the sensory hair cells and the auditory performance of mT/mG transgenic mice. Auditory brainstem responses and distortion product otoacoustic emissions revealed that adult mT/mG homozygous mice are profoundly deaf, whereas heterozygous mice present high frequency loss. We explore whether this line would be useful for studying and visualizing the membrane of auditory hair cells by airyscan super-resolution confocal microscopy. Membrane localization of the reporter was observed in hair cells of the cochlea, facilitating imaging of both cell bodies and stereocilia bundles without altering cellular architecture or the expression of the integral membrane motor protein prestin. Remarkably, hair cells from mT/mG homozygous mice failed to uptake the FM1-43 dye and to locate TMC1 at the stereocilia, indicating defective mechanoelectrical transduction machinery. Our work emphasizes that precautions must be considered when working with reporter mice and highlights the potential role of the cellular membrane in maintaining functional hair cells and ensuring proper hearing.

Download Full-text