title: Gentamicin differentially alters cellular metabolism of cochlear hair cells as revealed by NAD(P)H fluorescence lifetime imaging.
abstract: Aminoglycoside antibiotics are implicated as culprits of hearing loss in more than 120,000 individuals annually. Research has shown that the sensory cells, but not supporting cells, of the cochlea are readily damaged and/or lost after use of such antibiotics. High-frequency outer hair cells (OHCs) show a greater sensitivity to antibiotics than high- and low-frequency inner hair cells (IHCs). We hypothesize that variations in mitochondrial metabolism account for differences in susceptibility. Fluorescence lifetime microscopy was used to quantify changes in NAD(P)H in sensory and supporting cells from explanted murine cochleae exposed to mitochondrial uncouplers, inhibitors, and an ototoxic antibiotic, gentamicin (GM). Changes in metabolic state resulted in a redistribution of NAD(P)H between subcellular fluorescence lifetime pools. Supporting cells had a significantly longer lifetime than sensory cells. Pretreatment with GM increased NAD(P)H intensity in high-frequency sensory cells, as well as the NAD(P)H lifetime within IHCs. GM specifically increased NAD(P)H concentration in high-frequency OHCs, but not in IHCs or pillar cells. Variations in NAD(P)H intensity in response to mitochondrial toxins and GM were greatest in high-frequency OHCs. These results demonstrate that GM rapidly alters mitochondrial metabolism, differentially modulates cell metabolism, and provides evidence that GM-induced changes in metabolism are significant and greatest in high-frequency OHCs.
authors: Drexel University, Department of Neurobiology and Anatomy, 2900 West Queen Lane, Philadelphia, Pennsylvania 19129, United States.
authors: Lyandysha V
authors: LV
authors: Zholudeva
authors: Creighton University, Department of Physics, 2500 California Plaza, Omaha, Nebraska 68178, United States.
authors: Kristina G
authors: KG
authors: Ward
authors: Creighton University, Department of Physics, 2500 California Plaza, Omaha, Nebraska 68178, United StatescCreighton University, Department of Biomedical Sciences, 2500 California Plaza, Omaha, Nebraska 68178, United States.
authors: Michael G
authors: MG
authors: Nichols
authors: Creighton University, Department of Biomedical Sciences, 2500 California Plaza, Omaha, Nebraska 68178, United States.
authors: Heather Jensen
authors: HJ
authors: Smith
mesh_terms: D000162:Acoustics; D000617:Aminoglycosides / Q000009:adverse effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D003051:Cochlea / Q000187:drug effects / Q000502:physiology; D005839:Gentamicins / Q000009:adverse effects*; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects*; D051379:Mice; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D009249:NADP / Q000737:chemistry*; D061848:Optical Imaging; D013016:Sound
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D009249:NADP