This project provides new knowledge of the auditory mechanisms of the inner ear through studies of the biochemistry, morphology, pharmacology and physiology of auditory sensory cells, supporting cells and neurons of the inner ear, using small mammals, bullfrogs and sharks. An immunocytochemical study of receptors in the cochlea is in progress. Immunological studies have been initiated to provide specific markers of cells of the organ of Corti. A study is in progress in which we seek to purify and characterize the enzyme for force generation during intracellular organelle translocation, preparing microtubules from bovine brain and translocator proteins from cultured Acanthamoeba. The possibility that outer hair cells may modulate the micromechanical properties of the hearing organ through mechanical feedback mechanisms led us to the following study, now in press in Nature. Isolated outer hair cells were prepared from the organ of Corti of guinea pig by non-enzymatic mechanical dissociation. Sinusoidal potential gradients were passed across such hair cells, causing oscillatory elongation and shortening of the outer hair cells and oscillatory movements of intracellular organelles as was directly visualized and measured from the video recorded images. Maximal responses were obtained when cells were longitudinally aligned with the direction of the electric field. The responses were unaffected by incubation of the cells with medium containing inhibitors of ATP production (dinitrophenol and iodoacetic acid). Responses were enhanced by lowering the ionic concentration. Cells with little movement in the standard medium reversibly showed robust movement after ionic dilution. Based on these experimental findings we proposed a novel mechanisms for mechanical changes in outer hair cells based on an elecro-osmotic effect and not dependent on conventional conractile processes.
