Abstract
Annually more than 100,000 people treated with lifesaving antibiotics develop hearing or balance disorders. Of the two types of cochlear sensory cells, inner hair cells (IHCs) are significantly more resilient than outer hair cells (OHCs) to acoustic trauma, age-related hearing loss, and antibiotic ototoxicity. Changes in the fluorescence lifetime of the metabolic intermediate NADH were measured in I/OHCs to determine if endogenous and antibiotic-induced differences in sensory cell mitochondrial metabolism exist. The dynamic range of NADH metabolism (maximum NADH oxidation and reduction) was greatest in high-frequency OHCs. Sodium cyanide redistributed NADH into different subcellular microenvironments in IHCs and OHCs. Pretreatment with the ototoxic antibiotic gentamicin (GM) altered the NaCN effect in I/OHCs. These initial descriptions of fundamental differences between IHC and OHC mitochondrial metabolism indicates how high-frequency OHCs are profoundly sensitive to a number of cochlear challenges including ototoxic antibiotics. Conducted at the Integrative Biological Imaging Facility at Creighton University, supported by the C.U. Medical School, NIH NCRR (5P20RR016469) and NIGMS (8P20GM103427). MN supported by R15 GM085776. KW and LZ supported by NIGMS (8P20GM103427). HJS supported by NIH NIDCD (RO3DC012109) and COBRE (8P20GM103471-09).
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