MOLECULAR DELINEATION OF THE COCHLEAR HAIR CELLS

  • Beisel, Kirk (PI)

Project: Research project

Project Details

Description

DESCRIPTION: (Adapted from the Investigator's Abstract) Our long term goal is
to understand how cochlear hair cells function as an effective frequency
analyzer of the peripheral auditory system. The goals of this proposal are to
identify members of the voltage-gated ion channel superfamily expressed in
cochlear hair cells and to determine their spatial and temporal patterns of
expression in developmental and adult stages. These studies will seek to
correlate the anatomical maturation and neuronal innervation of the organ of
Corti with the functional maturation of the cochlear hair cells' receptor
potential and synaptic transmission. Our studies will focus on characterization
of the ion channels that shape the receptor potential at the molecular level.
These channels include the voltage-gated K+ (Kv) and Na+ (Scn) ion channels and
the inward rectifiers (Kir). The voltage-dependent Ca2+ (CACN) channels and
calcium-activated K+ channels (Kca), which are involved in cochlear hair cell
synaptic transmissions, will also be characterized. Initial gene expression
analysis of these ion channels will use degenerative gene-family and
gene-specific oligonucleotide primers to amplify cDNAs from cochlear, inner
hair cell, and outer hair cell cDNA libraries as well as single cell RT-PCR.
The first aim will be to characterize the hair cells' ion channels in normal
adult rats and mice at the molecular level using wholemount and section
preparations of the organ of Corti and applying probes directed at candidate
proteins (immunocytochemistry) and mRNA (in situ hybridization). Once the adult
spatial expression patterns are established, we will study the spatio-temporal
expression patterns in mice during a prenatal and neonatal time course to
determine acquisition time of these ion channels and to correlate these changes
with innervation and anatomical maturation. Lastly we will determine the
spatial pattern of ion channel expression in null mutant mice (Ngn-1, Ntrk2
(trkB), Ntf3 (Nt-3), Ntrk2+/Ntf3+/-, and Ntf3+-PDGF promoter-Ntf3+) to
elucidate the relationship between innervation and electrophysiological
maturation. Identification of molecular elements involved in the receptor
potential and synaptic transmission of cochlear hair cells should lead to a
greater understanding of inner ear function and contribute to our comprehension
of auditory pathologies.
StatusFinished
Effective start/end date1/1/0012/31/03

Funding

  • National Institute on Deafness and Other Communication Disorders: $296,618.00
  • National Institute on Deafness and Other Communication Disorders: $294,187.00
  • National Institute on Deafness and Other Communication Disorders: $116,483.00
  • National Institute on Deafness and Other Communication Disorders: $186,528.00

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