ENDOCYTOSIS OF AMINOGLYCOSIDE ANTIBIOTICS IN SENSORY HAIR-CELLS

Immuno-gold electron microscopy was used to assess the uptake pathways of aminoglycoside antibiotic kanamycin (KM) in sensory hair cells. Ac cumulation of gold particles was evident on the plasma membrane as wel l as in large smooth vesicles beneath the apical surfaces of hair cell s 12 h after a systemic administration of KM. Immune-gold was exclusiv ely localized in the vesicles 27 h post-injection. Cationic ferritin, a membrane-bound insoluble marker, was colocalized with KM in the vesi cle structures after their simultaneous in vitro application. These re sults strongly suggest that KM is taken up into sensory hair cells via receptor-mediated endocytosis at their apical surfaces. In addition, the profound time lag between KM uptake and hair cell death suggests i nvolvement of targeting mechanisms in cytotoxic signalling pathways of the drugs.