Prestin-based outer hair cell electromotility in knockin mice does not appear to adjust the operating point of a cilia-based amplifier.
The remarkable sensitivity and frequency selectivity of the mammalian cochlea is attributed to a unique amplification process that resides in outer hair cells (OHCs). Although the mammalian-specific somatic motility is considered a substrate of cochlear amplification, it has also been proposed that somatic motility in mammals simply acts as an operating-point adjustment for the ubiquitous stereocilia-based amplifier. To address this issue, we created a mouse model in which a mutation (C1) was introduced into the OHC motor protein prestin, based on previous results in transfected cells. In C1/C1 knockin mice, localization of C1-prestin, as well as the length and number of OHCs, were all normal. In OHCs isolated from C1/C1 mice, nonlinear capacitance and somatic motility were both shifted toward hyperpolarization, so that, compared with WT controls, the amplitude of cycle-by-cycle (alternating, or AC) somatic motility remained the same, but the unidirectional (DC) component reversed polarity near the OHC's presumed in vivo resting membrane potential. No physiological defects in cochlear sensitivity or frequency selectivity were detected in C1/C1 or C1/+ mice. Hence, our results do not support the idea that OHC somatic motility adjusts the operating point of a stereocilia-based amplifier. However, they are consistent with the notion that the AC component of OHC somatic motility plays a dominant role in mammalian cochlear amplification.
Gao
Jiangang
J
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Wang
Xiang
X
Wu
Xudong
X
Aguinaga
Sal
S
Huynh
Kristin
K
Jia
Shuping
S
Matsuda
Keiji
K
Patel
Manish
M
Zheng
Jing
J
Cheatham
Maryann
M
He
David Z
DZ
Dallos
Peter
P
Zuo
Jian
J
D000595:Amino Acid Sequence; D000669:Amplifiers, Electronic; D000818:Animals; D001307:Auditory Perception; D001483:Base Sequence; D002460:Cell Line; D002469:Cell Separation; D048430:Cell Shape; D002923:Cilia / Q000378:metabolism; D004594:Electrophysiology; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020409:Molecular Motor Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D017711:Nonlinear Dynamics; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D020409:Molecular Motor Proteins; C498720:Pres protein, mouse; D011506:Proteins