The initial goal of this project is to investigate the structure and function of mammalian outer hair cell laminated cisternae. Laminated cisternae are uniquely mammalian organelles that are thought to play a role in outer hair cell electromotility. Cat and human outer hair cells have a single laminated cisterna in contrast to the multiple layers of the guinea-pig outer hair cell. The ultrastructural organization of cat and human laminated cisternae are examined in isolated cells and their motility measured. If the electromotile response is similar for cat and human and less than the response of guinea-pig outer hair cells then a link between the structure and function of the laminated cisternae is supported. A long-term goal of the project is to investigate the voltage and ligand dependent properties of membrane channels in both outer and inner hair cells. These studies explore the Structure-function relation between ion channels and functionally significant membrane permeability changes. Stereocilia mediated receptor potentials are shaped by voltage and ion dependent membrane channels. Membrane conductance changes therefore regulate outer hair cell electromotility and inner hair cell neurotransmitter release. It is important to determine if the membrane conductance differences between inner and outer hair cells reported for the guinea-pig are also found in other mammalian species, particularly human. Shape changes are evoked using whole cell electrical stimulation (and recording) in voltage clamp. Movements are measured with photodiode arrays or by the analysis of video images. Changes in cell turgor affect rapid electromotility in outer hair cells. The mechanisms of outer hair cell volume and turgor pressure regulation are investigated by measuring the effect of aspirin, aminoglycosides, polyamines and simple sugars. These studies provide direct measures of human hair cell physiology and their response to ototoxic drugs. In addition to the direct application of the results to human hearing and its disorders the project provides highly relevant research training for hearing scientists, particularly physician-scientists.
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