In vertebrate outer hair cells, synaptic inhibition is achieved by the activation of nicotinic (ionotropic) acetylcholine (ACh) receptors that usually mediate excitatory postsynaptic responses else where in the nervous system. Calcium (Ca++) influx through these ACh receptors leads to activation of calcium dependent potassium channels. This proposal aims to explore the intracellular pathways that couple the ionotropic hair cell ACh receptors to inhibition. A combination of electrophysiology and molecular biology techniques will be used to test whether an IP3-sensitive calcium store may be involved in such a process. Since phospholipase C (PLC) catalyses the synthesis of IP3, the role of PLC in cholinergic inhibition will be examined next by employing pharmacological agents. RT-PCR and immunohistochemistry will used to determine the pattern of expression of the different PLC sub-types in the cochlea. Data from this research will help elucidate the molecular mechanisms by which ACh released from the olivo-cochlear bundle mediates hair cell inhibition.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DC005686-02
Application #
6640531
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Sklare, Dan
Project Start
2002-09-01
Project End
2004-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
2
Fiscal Year
2003
Total Cost
$46,420
Indirect Cost
Name
Johns Hopkins University
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218