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Outer Hair Cell Electromotility
measured in cadaver ears. Shyam Khanna in New York City soon confirmed these observations using laser interferom- etry (Khanna and Leonard, 1982).
The most direct demonstration of a mechanism in the co- chlea that could generate mechanical energy was the dis- covery of otoacoustic emissions by David Kemp in London late in the 1970s. He initially reported the presence of sound coming from the cochlea, now called otoacoustic emissions, after stimulation with a brief sound (Kemp, 1978). He then showed that some ears produce sound without being stimu- lated (for historical details, see Kemp, 2008). This was direct evidence of Gold’s active process. Measuring otoacoustic emissions has become an important tool for assessing hear- ing loss, even in newborns and unresponsive patients. Steve Neely, Duck Kim, Egbert de Boer, David Mountain, and oth- ers began to include a source of mechanical energy in their theoretical models of cochlear mechanics. In 1983, Hallowell Davis, a senior hearing scientist at the Central Institute for the Deaf in St. Louis, MO, coined the term “cochlear ampli- fier” for the active process. The cellular basis of the cochlear amplifier was a puzzle that was soon resolved.
The First Observation of
Outer Hair Cell Electromotility
The discovery of OHC electromotility took place late in the morning on December 3, 1982, in the medical school laboratories of Daniel Bertrand and Charles Bader at the University of Geneva where I was taking a sabbatical from the University of Florida. Charlie and Daniel had pioneered techniques to dissect, isolate, and record photoreceptors to characterize ionic movement across their membranes. We had met at a photoreceptor meeting in Sicily a year earlier. I attended the meeting because of the many structural and functional similarities between vertebrate photoreceptors and hair cells. I had described these similarities and pro- posed isolated hair cell studies in a review paper that was published the same year as the discovery (Brownell, 1982). Several months were required to optimize the primary cell culture procedures for hair cells. OHCs proved easier to iso- late, most likely because of the absence of supporting cells on their lateral walls. We began voltage-clamp attempts in October. The homemade optics, amplifiers, and data-collec- tion programs required a team effort to pull off the experi- ments. We were using micropipettes to make intracellular recordings (whole cell patch-clamp techniques were just be- ing developed). The standard routine was for Charlie to ad- vance the electrode while looking at it and the cell through a
microscope. Daniel was poised over the electronics looking for the tell-tale voltage shift that would indicate we were in- side the cell. I was responsible for dissecting the cochlea and isolating the cells, after which I would sit behind the others and record the results in the lab notebook.
A common technique at the time was to “buzz” the electrode when its tip was positioned on the cell membrane. The buzz was achieved by throwing the amplifier headstage into elec- trical oscillation. For reasons that are still not clear, the buzz would push the tip of the electrode through the membrane. The pivotal moment occurred when Daniel buzzed and I could see Charlie’s back and shoulders jerk in a classic star- tle response to what he had seen through the microscope. Still looking though the microscope, Charlie called for an- other buzz, and his body responded with another somewhat smaller response. At that point, Charlie turned around and said “We have a problem.” Daniel and I then took turns look- ing at OHC electromotility as Charlie buzzed. Proving that the electrically evoked length change was not an artifact was the “problem” to which Charlie was referring.
The remainder of my sabbatical was given over to OHC electromotility. We eliminated potential artifacts and fur- ther characterized the phenomenon. It was only after I es- tablished that hyperpolarization caused elongation and de- polarization caused shortening was I confident that OHC electromotility was not an artifact. For several months, we had no equipment for recording the conspicuous move- ments and visiting scientists were asked to sign our lab book acknowledging that they saw the movements. I eventu- ally captured the movements using video microscopy (see http://acousticstoday.org/OHCEM1), eliminating the need for affidavits, and we published our findings (Brownell 1983; Brownell et al., 1985).
The OHC was quickly identified as Gold’s piezoelectric-like energy source. The modelers now had a cellular locus for the cochlear amplifier. The fact that OHC axial length changes would lose energy if they contacted adjacent cells explained the large extracellular spaces around the OHCs. I had specu- lated about an electromechanical mechanism in my review paper (Brownell, 1982) that was based on the synaptic activ- ity in the base of the OHC. Looking through the microscope and later examining the videotapes revealed that the active process was in the lateral wall, thereby suggesting a function for the structurally unique organization of the lateral wall (Figure 4). Other work going on at the same time identified the battery that powers the process.
24 | Acoustics Today | Spring 2017