This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Previous studies demonstrate that Ca2+ and K+ channel conductances confer ditinct properties to vestibular and auditory hair cells. As nitric oxide synthase is localized in the efferent nerve terminals of the mammalian inner ear we hypothesized that nitric oxide (NO) acts to modulate these ionic currents and thau the gain of the hair cell''s activity profile. Currently we have focussed on the calcium conductance. Using the NO design of self-referencing sensor developed at the BioCurrents Research Center we have shown: 1. Acetylcholine, the putative efferent nerotransmitter, release NO from the saccula 2. NO applied in solutions reduced the whole cell Ca2+ currents as well as the single channel Ca2+ current in hair cells 3. Reduced Ca2+ conductance results from cells held in the open probability state 4. The effects of NO are reversible using dithiothreitol We conclude that by reducing the Ca2+ influx and decreasing neurotransmitter release NO modulates the gain of the hair cell. The major activity with this subproject has been a visit from BRC engineer R. Sanger to reconfigure and update this off campus site.
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