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. The inability to detect odors is a very real handicap. A diminished sense of smell, which is quite common in the elderly, can lead to malnutrition. A number of medical problems, such as cystic fibrosis and Alzheimer's disease, can cause olfactory dysfunction. Central to the understanding of the olfactory system is determining how the inputs, the primary olfactory sensory neurons (OSNs) function; this is our long-term goal. Chloride fluxes and intracellular chloride levels are extremely important in determining the ultimate outcome of the exposure of an olfactory neuron to odor: is it stimulated or inhibited? Chloride levels play an essential role, but because Cl- comes in late in the signal transduction pathway, less attention has been focused on it compared to other second messengers. We are testing the hypothesis that Cl- homeostasis is essential to olfactory neuron function and that changing [Cl]i alters odor responses. Progress: Results from MEQ fluorescence imaging experiments indicated that a wide range of [Cl]i exist in isolated OSNs and that [Cl]i levels remain constant unless the cell is stimulated. Inhibition of either of the two Cl transporters, NKCC1 and KCC2 can alter the odor response although there appears to be a 3rd Cl transporter whose effects were observed when NKCC1 activity was decreased. Immunocytochemistry on isolated OSNs showed the NKCC1 and KCC2 are located on the cilia and dentritic knob, the site of odor transduction. How these Cl transporters are regulated remains unclear but [Cl]i plays an integral role in odor transduction and probably determines if an odor response is excitatory or inhibitory.
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