Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier

Abstract

Hearing sensitivity in mammals is enhanced by more than 40 dB (that is, 100-fold) by mechanical amplification thought to be generated by one class of cochlear sensory cells, the outer hair cells. In addition to the mechano-electrical transduction required for auditory sensation, mammalian outer hair cells also perform electromechanical transduction, whereby transmembrane voltage drives cellular length changes at audio frequencies in vitro. This electromotility is thought to arise through voltage-gated conformational changes in a membrane protein, and prestin has been proposed as this molecular motor. Here we show that targeted deletion of prestin in mice results in loss of outer hair cell electromotility in vitro and a 40-60 dB loss of cochlear sensitivity in vivo, without disruption of mechano-electrical transduction in outer hair cells. In heterozygotes, electromotility is halved and there is a twofold (about 6 dB) increase in cochlear thresholds. These results suggest that prestin is indeed the motor protein, that there is a simple and direct coupling between electromotility and cochlear amplification, and that there is no need to invoke additional active processes to explain cochlear sensitivity in the mammalian ear.

Resting Potential and Submembrane Calcium Concentration of Inner Hair Cells in the Isolated Mouse Cochlea Are Set by KCNQ-Type Potassium Channels

“…A contribution of central auditory pathways, in which neuronal KCNQ4 expression is found, has been proposed (Jentsch, 2000;Kharkovets et al, 2000). Alternatively, a more generalized degeneration of the organ of Corti, including OHCs and IHCs, may lead to severe hearing loss, as recently observed in a mouse model bearing a targeted gene deletion of the OHC-specific protein prestin (Liberman et al, 2002).…”

Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV

“…Outer hair cells (OHCs) connect only to poorly defined type II neurons. Their main function is to amplify the vibration produced by sound by as much as 60 decibels (dB) in a frequency-specific manner, and they are essential for frequency discrimination 9 (important in speech perception). Most deafness genes known to affect hair cell function are expressed in both cell types, so, in general, gene therapy strategy should target both IHCs and OHCs.…”

Fabrication, dynamics, and electrical properties of insulated scanning probe microscopy probes for electrical and electromechanical imaging in liquids

“…[16][17][18] From the data in Table I, the increase in effective mass for tip 1 is 22.9% and for 55% for tip 2. From the known densities of Si and SiO 2 ͑2.33 and 2.2 g / cm 3 , respectively͒, the increases in thickness are 24.2% and 58.2%, respectively. For the compound beam formed by a central beam of width w 1 and thickness h 1 surrounded by an external shell of width w 2 and thickness h 2 , the effective stiffness is…”

“…The ubiquity of electromechanical phenomena in biological and biomolecular systems ranging from voltage controlled muscular contractions 1 to cell electromotility, 2 ion channels, and electromotor proteins 3 necessitates probing of these phenomena on the tissue, cellular, subcellular, and molecular levels. Scanning probe microscopy ͑SPM͒ studies of biological systems necessitate the use of a liquid environment to maintain a native environment for biomolecules and cells to control tip-surface forces and to eliminate capillary interactions.…”