Sensory transduction and adaptation in inner and outer hair cells of the mouse auditory system.

Auditory function in the mammalian inner ear is optimized by collaboration of two classes of sensory cells known as inner and outer hair cells. Outer hair cells amplify and tune sound stimuli that are transduced and transmitted by inner hair cells. Although they subserve distinct functions, they share a number of common properties.

Dominant-negative inhibition of M-like potassium conductances in hair cells of the mouse inner ear.

Sensory hair cells of the inner ear express multiple physiologically defined conductances, including mechanotransduction, Ca(2+), Na(+), and several distinct K(+) conductances, all of which are critical for normal hearing and balance function. Yet, the molecular underpinnings and their specific contributions to sensory signaling in the inner ear remain obscure. We sought to identify hair-cell conductances mediated by KCNQ4, which, when mutated, causes the dominant progressive hearing loss DFNA2.

The very large G-protein-coupled receptor VLGR1: a component of the ankle link complex required for the normal development of auditory hair bundles.

Sensory hair bundles in the inner ear are composed of stereocilia that can be interconnected by a variety of different link types, including tip links, horizontal top connectors, shaft connectors, and ankle links. The ankle link antigen is an epitope specifically associated with ankle links and the calycal processes of photoreceptors in chicks. Mass spectrometry and immunoblotting were used to identify this antigen as the avian ortholog of the very large G-protein-coupled receptor VLGR1, the product of the Usher syndrome USH2C (Mass1) locus.

Fast adaptation in vestibular hair cells requires myosin-1c activity.

In sensory hair cells of the inner ear, mechanical amplification of small stimuli requires fast adaptation, the rapid closing of mechanically activated transduction channels. In frog and mouse vestibular hair cells, we found that the rate of fast adaptation depends on both channel opening and stimulus size and that it is modeled well as a release of a mechanical element in series with the transduction apparatus. To determine whether myosin-1c molecules of the adaptation motor are responsible for the release, we introduced the Y61G mutation into the Myo1c locus and generated mice homozygous for this sensitized allele.

Treatment with the antiepileptic drugs phenytoin and gabapentin ameliorates seizure and paralysis of Drosophila bang-sensitive mutants.

Drosophila bang-sensitive (bs) mutants exhibit a stereotypic seizure and paralysis following exposure to mechanical shock. In a physiological preparation, seizures and failures corresponding to the defective behavior are observed in response to high frequency stimulation. The amplitude of the stimulus necessary to produce bs behavior, or seizure threshold, varies with bs mutant and its gene dosage.