O the difference of intrinsic susceptibility of cochlea to aminoglycosides. Contemplating that hair cells in the basal turn are severely impacted, whereas hair cells in the apex usually are not affected when exposed to an equal level of aminoglycosides,1,3 a specific underlying difference in intrinsic susceptibility toward drugs may possibly exist. Interestingly, Sha et al.4 supported this possibility by demonstrating that the levels of reduced 635702-64-6 web glutathione, a essential reactive oxygen species scavenger, are larger in the apex than those of OHCs at the base; thereby, OHCs at the apex are intrinsically more resistantVestibulocochlear Research Center, Center for Metabolic Function Regulation and Division of Microbiology, Wonkwang University College of Medicine, Iksan, Jeonbuk, South Korea Correspondence: Professor H-S So, Division of Microbiology, Wonkwang University School of Medicine, 344-7 Shinyong-dong, Iksan, Jeonbuk 570-749, South Korea. E-mail: [email protected] or Professor R Park, Division of Microbiology, Wonkwang University College of Medicine, 344-2 Shinyong-dong, Iksan, Jeonbuk 570-749, South Korea. E-mail: [email protected] 1These two authors contributed equally to this work. 2Present address: Center for Neuroscience, Department of Anesthesiology and Pain Medicine, System in Communication Science, School of Medicine, University of California, Davis, Davis, CA, USA. 3Present address: Division of Cell Biology and Genetics, House Analysis Institute, Los Angeles, CA, USA. Received 12 December 2012; accepted 9 JanuaryTRPV channels in gentamicin uptake J-H Lee et alto free-radical damage than those at the base. Nonetheless, there might be a difference of gentamicin uptake by hair cells at the basal or apical turn on the cochlea, and this difference might influence the susceptibility of hair cells to gentamicin top to the base-to-apex gradient ototoxicity. It has been proposed that endocytosis is among the mechanisms of aminoglycoside uptake in the hair cell apical membrane.5,six Internalized aminoglycosides are transported to lysosomes where they accumulate and bring about hair cell apoptosis more than time.7 Generally, endocytosis is temperature dependent in euthermic birds and mammals and slows down at hypothermic temperatures.8 However, rapid aminoglycoside uptake and toxicity happen at room temperature as well as at 4 1C in vitro,91 additional supporting the possibility that aminoglycosides permeate by way of nonselective cation channels. This probably includes 153559-49-0 Biological Activity transient receptor prospective (TRP) cation channels from the subfamily V, for instance TRP vanilloid 1 (TRPV1) and TRP vanilloid two (TRPV4) for the reason that regulators of these channels modulate aminoglycoside uptake.11,12 While zebrafish don’t include a cochlea or outer ear,13,14 hair cells in zebrafish neuromasts, which are equivalent in structure and function for the inner ear hair cells in mammals, execute vestibular and auditory functions.15,16 The neuromasts are arranged inside a stereotypical pattern along the anterior lateral lines from the head, body and posterior lateral lines in the tail. Live hair cells might be visualized effortlessly in vivo in transparent embryos by staining with 2-(4-(dimethylamino)styryl)-N-ethylpyridinium iodide (DASPEI), a fluorescent styryl dye.179 The optical clarity of the zebrafish offers positive aspects for high-throughput morphological and functional analyses of hair cells following drug treatment. The use of gentamicin conjugated to fluorescent Texas Red (GTTR) shows the intracellular localization of thi.