Biomedical subjects
Publications and source records attributed to Mary Ann Cheatham.
In non-mammalian, hair cell-bearing sense organs amplification is associated with mechano-electric transducer channels in the stereovilli (commonly called stereocilia). Because mammals possess differentiated outer hair cells (OHC), they also benefit from a novel electromotile process, powered by the motor protein, prestin. Here we consider new work pertaining to this protein and its potential role as the mammalian cochlear amplifier.
Efferent nerve fibers form chemical synapses at the bases of outer hair cells (OHC), with acetylcholine (ACh) being their principal neurotransmitter. The activation of ACh receptors on OHCs is known to influence cochlear function. These efferent effects exhibit an unusual pharmacology and are generally known to be inhibitory. Recent evidence suggests that an ACh receptor subunit, known as alpha9, plays a dominant role in mediating the olivocochlear neurotransmission to OHCs. In this investigation, we attempt to determine the possible role(s) of the alpha9 subunit in regulating OHC function by examining OHC electromotility and compound action potentials (CAP) in mice carrying a null mutation for the alpha9 gene. Results indicate that cochlear sensitivity, based on CAP thresholds, is similar for homozygous mutant and wild-type mice. Electromotility is also present in OHCs, independent of whether the alpha9 subunit is present or absent.
Because reelin and prestin genes are located close together on mouse chromosome 5, reelin homozygous mutant mice were compared with littermate controls. Experiments were designed to determine if the deletion in the reeler mouse affects the coding and/or regulatory regions for the expression of prestin, the outer hair cell motor protein. Data indicate that homozygous reeler mice express prestin mRNA and protein, as do controls. Cochlear sensitivity, determined using compound action potential thresholds measured at the round window, is also similar. Hence, threshold shifts previously observed in auditory brainstem responses are not due to cochlear problems. Because prestin expression is not affected in reeler mice, prestin's coding region, as well as any regulatory elements, is predicted to lie in the 17 kb that separate prestin's exon 1 from the end of the deletion.
The thresholds of compound action potentials evoked by tone pips were measured in the cochleae of anesthetized gerbils, both in adults and in neonates aged 14, 16, 18, 20 and 30 days, using round-window electrodes. Stapes vibrations were also measured, using a laser velocimeter, in many of the same ears of adults and neonates aged 14, 16, 18 and 20 days to assess cochlear sensitivity in isolation from middle ear effects and to circumvent problems associated with calibration of acoustic stimuli at high frequencies. Whether referenced to sound pressure level in the ear canal or stapes vibration velocity, thresholds in adults were roughly uniform in the entire range of tested frequencies, 1.25-38.5 kHz. In neonates, thresholds decreased systematically as a function of age, with the largest reductions occurring at the highest frequencies. Thresholds remained slightly immature at all frequencies 30 days after birth. The results for adult gerbils are consistent with the recent finding that basilar-membrane responses to characteristic frequency tones normalized to stapes vibrations are as sensitive at sites near the round window as at more apical sites. The results for neonates confirm that the extreme basal region of the cochlea is the last to approach maturity, with substantial development occurring between 20 and 30 days after birth.