Mon. Jul 15th, 2024

O the difference of intrinsic susceptibility of cochlea to aminoglycosides. Considering that hair cells at the basal turn are severely impacted, whereas hair cells in the apex are usually not affected when exposed to an equal volume of aminoglycosides,1,three a particular underlying difference in intrinsic susceptibility toward drugs may exist. Interestingly, Sha et al.four supported this possibility by demonstrating that the levels of decreased glutathione, a critical reactive oxygen species scavenger, are greater at the apex than those of OHCs in the base; thereby, OHCs at the apex are intrinsically much more resistantVestibulocochlear Research Center, Center for Metabolic Function Regulation and Department of Microbiology, Wonkwang University School of Medicine, Iksan, Jeonbuk, South Korea Correspondence: Professor H-S So, Department 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, Division of Anesthesiology and Discomfort Medicine, Program in Communication Science, College of Medicine, University of California, Davis, Davis, CA, USA. 3Present address: Division of Cell Biology and Genetics, House Investigation Institute, Los Angeles, CA, USA. Received 12 December 2012; accepted 9 JanuaryTRPV channels in gentamicin uptake J-H Lee et alto free-radical harm than those at the base. However, there may perhaps be a difference of gentamicin uptake by hair cells at the basal or apical turn with the cochlea, and this difference may possibly have an effect on the susceptibility of hair cells to gentamicin top for the base-to-apex gradient ototoxicity. It has been proposed that endocytosis is amongst the mechanisms of aminoglycoside uptake at the hair cell apical membrane.five,six Internalized aminoglycosides are transported to lysosomes exactly where they accumulate and cause hair cell apoptosis more than time.7 Generally, endocytosis is temperature dependent in euthermic birds and mammals and slows down at hypothermic temperatures.eight Nevertheless, fast aminoglycoside uptake and toxicity take place at area temperature as well as at 4 1C in vitro,91 further supporting the possibility that aminoglycosides permeate via nonselective cation channels. This most likely entails transient receptor potential (TRP) cation channels of the subfamily V, like TRP vanilloid 1 (TRPV1) and TRP vanilloid two (TRPV4) because regulators of these channels modulate aminoglycoside uptake.11,12 Even though zebrafish don’t contain a cochlea or outer ear,13,14 hair cells in zebrafish neuromasts, which are related in structure and function to 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 with the tail. Live hair cells could be visualized simply in vivo in transparent embryos by staining with 2-(4-(dimethylamino)styryl)-N-ethylpyridinium iodide ( DASPEI), a fluorescent Stampidine Epigenetic Reader Domain styryl dye.179 The optical clarity with the zebrafish offers benefits for high-throughput morphological and functional analyses of hair cells following drug treatment. The usage of gentamicin conjugated to fluorescent Texas Red (GTTR) shows the intracellular localization of thi.