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Title: Xyloside primed glycosaminoglycans alter hair bundle micromechanical coupling and synaptic transmission: Pharmacokinetics

Glycosaminoglycans (GAGs) are ubiquitous in the inner ear, and disorders altering their structure or production often result in debilitating hearing and balance deficits. The specific mechanisms responsible for loss of hair-cell function are not well understood. We recently reported that introduction of a novel BODIPY conjugated xyloside (BX) into the endolymph primes fluorescent GAGs in vivo [6, 15]. Confocal and two-photon fluorescence imaging revealed rapid turnover and assembly of a glycocalyx enveloping the kinocilia and extending into the cupula, a structure that presumably serves as a mechanical link between the hair bundle and the cupula. Extracellular fluorescence was also observed around the basolateral surface of hair cells and surrounding afferent nerve projections into the crista. Single unit afferent recordings during mechanical hair bundle stimulation revealed temporary interruption of synaptic transmission following BX administration followed by recovery, demonstrating an essential role for GAGs in function of the hair cell synapse. In the present work we present a pharmacokinetic model to quantify the time course of BX primed GAG production and turnover in the ear.
Authors:
;  [1] ; ; ;  [2] ;  [2] ;  [3] ;  [1] ;  [3] ;  [3] ;  [3]
  1. Bioengineering, University of Utah, Salt Lake City, Utah (United States)
  2. Medicinal Chemistry, University of Utah, Salt Lake City, Utah (United States)
  3. (United States)
Publication Date:
OSTI Identifier:
22494501
Resource Type:
Journal Article
Resource Relation:
Journal Name: AIP Conference Proceedings; Journal Volume: 1703; Journal Issue: 1; Conference: 12. international workshop on the mechanics of hearing, Cape Sounio (Greece), 23-29 Jun 2014; Other Information: (c) 2015 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSICS; AUDITORY ORGANS; FLUORESCENCE; HAIR; IN VIVO; PHOTONS; STIMULATION