Page 28 - 2017Spring

Outer Hair Cell Electromotility
Displacement Currents and
the Motor Gets a Protein
Passive OHC length changes resulting from mechanical stretch or electrically evoked length changes produce a “dis- placement” current. The electrically evoked current is ca- pacitive in nature because it is out of phase with the stimu- lus voltage. This reactive (nonohmic) current is vulnerable to manipulations such as aspirin or loss of turgor pressure that modify electromotility (Santos-Sacchi, 1991; Shehata et al., 1991). The magnitude of the displacement current varies with the membrane potential in a manner similar to the re- lationship between length change and membrane potential. The displacement current was found to require a membrane protein.
Peter Dallos and his colleagues found a protein important for electromotility at the the turn of the century (Zheng et al., 2000). The protein was discovered using a differential expression assay that showed that a protein was strongly expressed in OHCs. When they introduced the protein into other cell types, the large displacement currents charac- teristic of OHCs were also found. The investigators called the protein “prestin” from the Italian word “presto,” which indicates a rapid tempo in a muscial composition. Genetic manipulations that removed the protein altogether resulted in severe hearing loss and decreased otoacoustic emisisons (Liberman et al., 2002). These observations demonstrated that prestin plays an important role in the OHC electrome- chanical motor. The hearing science community was ecstatic with the protein.
The ability to insert prestin into the membranes of other cell types and to manipulate its molecular structure provided further evidence for the strength of the membrane protein interactions that underlie the OHC electromechanical mo- tor mechanism (Rajagopalan et al., 2006, 2007; Zhang et al., 2007). The precise role of the protein and its interaction with the motor elements in the OHC lateral wall remain to be identified. Tremendous strides have been made in char- acterizing the structural and molecular components that make up the motor elements, and we are getting closer to a complete biophysical understanding of OHC electromotility. New tools have been introduced that allow direct measurement of the length changes at acoustic frequencies in living animals (Gao et al., 2014; Ren et al., 2016). Analysis of these organ-level results will help clarify the cellular role of OHC electromotility.
Gold (1948) had proposed a piezoelectric-like energy source that was necessary to compensate for viscous damping re- sulting from the fluid environment that Cotugno (1775) had originally discovered. Spoendlin (1966) provided an impor- tant clue by showing that the OHCs did something other than convey information to the brain. OHC electromotility proved to be the piezoelectric-like source of mechanical en- ergy that acts as the cochlear amplifier to compensate for viscous damping in the fluid-filled cochlea. The end result is greater sensitivity and sharper tuning. Although we now know with reasonable certainty how the OHC contributes to hearing, we still don’t know the role of SGC2 fibers that could, in principle, convey information to the brain directly from the OHCs. And so, as is usually true in science, puzzles remain, and their resolution will bring even more puzzles.
Acknowledgments
The discovery of OHC electromotility was made possible by sabbatical funding from the University of Florida and research funding from Hoffman LaRoche. My subsequent investigations on the mechanisms involved and the writ- ing of this narrative have been funded by the citizens of the United States in the form of Research Grants R01-DC-00354 and R01-DC-02775 from the National Institute on Deafness and Other Communication Disorders, National Institutes of Health. My wife Nancy and editor Arthur Popper made many contributions to the style and delivery of the story.
Biosketch
Bill Brownell is a professor at the Bay- lor College of Medicine, Houston, TX, where he holds the Jake and Nina Ka- min Chair of Otorhinolaryngology. Pre- viously held appointments were at the University of Florida, Gainesville, FL, and the Johns Hopkins School of Medi-
cine, Baltimore, MD. He spent two years (1965-1966) teach- ing science and mathematics in Nigeria with the United States Peace Corps between his undergraduate training in physics and graduate training in physiology at the Univer- sity of Chicago, Chicago, IL. He is a Fellow of the Acoustical Society of America and a past president of the Association for Research in Otolaryngology. His main research focus is on the electromechanics of hearing.
26 | Acoustics Today | Spring 2017